New candidate SNPs for genetic association with Alzheimer's disease: a linkage disequilibrium analysis for the FCGRIIB and PILRA genes

Background Two new SNPs have been recently associated to Alzheimer's disease in African American populations: FCGRIIB rs1050501 C/T, and PILRA rs1859788 A/G. The risk of Alzheimer's disease in FCGRIIB C and PILRA A allele carriers is three times higher than in non-carriers. However, the association between these and other single nucleotide polymorphisms (SNPs) has not been assessed. Methods Linkage disequilibrium analysis, with r= 0.8 as a threshold value, was used to impute new candidate SNPs, on genomic data from both genes in 26 populations worldwide (n= 2504) from the 1000Genomes database. Results Four SNPs (rs13376485, rs3767640, rs3767639 and rs3767641) were linked to rs1050501 and one (rs2405442) to rs1859788 in the whole sample. Conclusions Five novel SNPs could be associated with Alzheimer's disease susceptibility and play a causal role, even if none of them are exon variants since their potential roles in the regulation of gene expression.

Antecedentes Recientemente se han asociado dos nuevos polimorfismos de un solo nucleótido (SNP) a la enfermedad de Alzheimer en poblaciones afroamericanas: FCGRIIB rs1050501 C/T, y PILRA rs1859788 A/G. El riesgo de enfermedad de Alzheimer en los portadores de los alelos FCGRIIB C y PILRA A es tres veces mayor que en los no portadores. Sin embargo, no se ha evaluado la asociación entre estos y otros SNP. Métodos Se utilizó el análisis de desequilibrio de ligamiento, con r2= 0,8 como valor umbral, para imputar nuevos SNPs candidatos, sobre datos genómicos de ambos genes en 26 poblaciones de todo el mundo (n= 2504) de la base de datos 1000Genomes. Resultados Cuatro SNPs (rs13376485, rs3767640, rs3767639 y rs3767641) se vincularon al rs1050501 y uno (rs2405442) al rs1859788 en toda la muestra. Conclusiones Cinco nuevos SNP podrían estar asociados con la susceptibilidad a la enfermedad de Alzheimer y desempeñar un papel causal, aunque ninguno de ellos sea una variante de exón, dado su papel potencial en la regulación de la expresión génica.

Alteraciones genéticas asociadas a la enfermedad de Parkinson y Alzheimer: evolución y respuesta al tratamiento / Genetic Alterations Associated with Parkinson's and Alzheimer's Disease: Evolution and Response to Treatment

La enfermedad de Parkinson y Alzheimer son las enfermedades neurodegenerativas más frecuentes a nivel mundial. Tienen etiología multifactorial, entre ellas, la genética; y son motivo de interés en la investigación científica actual. Se realizó una revisión narrativa con el objetivo de determinar las alteraciones genéticas asociadas a estas patologías, además su influencia en la evolución y respuesta al tratamiento de ellas. Se consultaron artículos originales, revisiones bibliográficas, sistemáticas, metaanálisis en inglés y español, con fecha de publicación entre el 1 enero de 2018 y el 20 de mayo de 2023, en bases como PubMed y Medline. Se utilizaron los términos MeSH «Alzheimer Disease¼, «Parkinson Disease¼, «Drug Therapy¼ y «Mutations¼. El riesgo hereditario para la enfermedad de Parkinson suele ser poligenético, sin embargo, existen genes relacionados con mutaciones monogénicas. Se identifican alteraciones en genes de α-sinucleína, glucocerebrosidasa y quinasa 2 rica en leucina que se relacionan con mayor riesgo de desarrollar Parkinson, además de variaciones en el cuadro clínico y edad de inicio de síntomas. En cuanto a la enfermedad de Alzheimer, las alteraciones en los genes de la proteína precursora amiloide, presenilina 1 y 2 se relacionan con la forma familiar de la enfermedad; por otra parte, las de apolipoproteína E4 se han identificado en la forma esporádica, por lo que se consideran como el factor de riesgo genético más importante para su desarrollo

Parkinson's and Alzheimer's are the most frequent neurodegenerative diseases worldwide. They have a multifactorial etiology, including genetics, and are of interest in current scientific research. A narrative review was carried out with the aim of determining the genetic alterations associated with these pathologies, as well as their influence on their evolution and response to treatment. Original articles, literature reviews, systematic reviews, meta-analyses in English and Spanish, with publication date between January 1, 2018 and May 20, 2023, were consulted in databases such as PubMed and Medline. MeSH terms "Alzheimer Disease", "Parkinson Disease", "Drug Therapy" and "Mutation" were used. Hereditary risk for Parkinson's disease is usually polygenetic, however, there are genes related to monogenic mutations. Alterations in α-synuclein, glucocerebrosidase and leucine-rich kinase 2 genes have been identified that are related to an increased risk of developing Parkinson's disease, in addition to variations in the clinical picture and age of symptom onset. As for Alzheimer's disease, alterations in the genes of the amyloid precursor protein, presenilin 1 and 2 are related to the familial form of the disease; on the other hand, those of apolipoprotein E4 have been identified in the sporadic form, and are therefore considered to be the most important genetic risk factor for its development

Ayuno intermitente y restricción calórica como tratamiento coadyuvante en enfermedad de Alzheimer y esclerosis múltiple / Intermittent Fasting and Caloric Restriction as an Adjunctive Treatment in Alzheimer's Disease and Multiple Sclerosis

Las enfermedades de Alzheimer y esclerosis múltiple son neurodegenerativas, con tratamientos complejos y de costos elevados, orientados a disminuir la progresión de la sintomatología. Sin embargo, a causa de la falta de terapias adecuadas y de los posibles efectos adversos ocasionados por tratamientos de primera línea, es necesario implementar mejores abordajes terapéuticos complementarios que no produzcan mayores efectos secundarios y mejoren la sintomatología de dichas patologías. La restricción calórica y el ayuno intermitente han demostrado ser estrategias novedosas y beneficiosas en enfermedades neurodegenerativas, a través de mecanismos inmunitarios, metabólicos y fisiológicos. Con el objetivo de determinar el uso del ayuno intermitente y la restricción calórica como tratamiento coadyuvante en esclerosis múltiple y enfermedad de Alzheimer, se realizó una revisión narrativa de artículos originales en revistas científicas, en idiomas inglés y español, de 2018 a 2022. El uso de la restricción calórica y ayuno intermitente han generado cambios positivos produciendo disminución de estados proinflamatorios, estrés oxidativo y envejecimiento. Se consideran abordajes que modulan la progresión de la enfermedad y mejoran la función cognitiva por vías de señalización de monofosfato de adenosina cinasa, factor de crecimiento similar a la insulina y la enzima sirtuina, generando un efecto neuroprotector.

Alzheimer's disease and multiple sclerosis are neurodegenerative disorders with expensive and complex treatments aimed at reducing the progression of symptoms. However, due to the lack of adequate therapies and the possible adverse effects caused by first-line treatments, it's necessary to implement better complementary therapeutic approaches that do not produce major side effects and improve symptoms. Caloric restriction and intermittent fasting have been shown to be novel and beneficial strategies in neurodegenerative diseases, through immune, metabolic, and physiological mechanisms. To determine the use of intermittent fasting and caloric restriction as a new treatment in multiple sclerosis and Alzheimer's disease, a narrative review of original articles in both national and international scientific journals, in English and Spanish languages with no greater obsolescence than five years. The use of caloric restriction and intermittent fasting have generated positive changes, producing a decrease in pro-inflammatory states, oxidative stress, and aging. Approaches that modulate disease progression and improve cognitive function of adenosine monophosphate kinase, insulin-like growth factor, and sirtuin enzyme pathways are considered, generating a neuroprotective effect.

Factores de riesgo asociados al agravamiento clínico de los pacientes ingresados con enfermedad de Alzhéimer

Introducción: La principal causa de demencia degenerativa es la enfermedad de Alzhéimer. En la población cubana, una de cada cuatro personas de 65 años y más fallece por esta enfermedad u otra forma de demencia. Objetivo : Identificar los factores de riesgo asociados al agravamiento clínico de los pacientes ingresados con enfermedad de Alzhéimer en el Hospital Psiquiátrico Universitario Rene Vallejo Ortiz entre enero de 2013 y diciembre de 2022. Métodos: Se realizó un estudio observacional, descriptivo y transversal. El universo estuvo integrado por todos los pacientes ingresados en la mencionada institución asistencial y docente. La muestra no probabilística y a criterio de los autores la integraron 77 pacientes adultos con el diagnóstico de la enfermedad en el periodo de estudio señalado. Las historias clínicas fueron la fuente secundaria de información. Se utilizó estadística descriptiva e inferencial. La información se resumió en tablas y gráficos. Resultados: El 90,6 % presentaban más de 60 años y más de la mitad eran del sexo masculino (54,5 %). La mayoría de los pacientes presentaron diversos síntomas asociados. Lo trastornos de personalidad y orientación se constataron en el 75,3 % mientras que los de memoria en el 72,7 %. Conclusiones: El agravamiento clínico luego del ingreso hospitalario se acentuó en aquellos pacientes sin escolaridad, solteros, desocupados, con enfermedades cerebro vasculares y presencia de familias disfuncionales presentaron. Los pacientes anémicos o con signos de irritación cortical focal en región frontoparietal con generalización secundaria presentaron mayoritariamente un empeoramiento clínico.

Introduction: The main cause of degenerative dementia is Alzheimer's disease. In the Cuban population, one in four people aged 65 and over dies from this disease or another form of dementia. Objective: To identify the risk factors associated with the clinical worsening of patients admitted with Alzheimer's disease at the Rene Vallejo Ortiz University Psychiatric Hospital. Methods: An observational, descriptive and cross-sectional study was carried out. The universe was made up of all patients admitted to the aforementioned healthcare and teaching institution. The non-probabilistic sample and at the discretion of the authors was made up of 77 adult patients with the diagnosis of the disease in the indicated study period between January 2013 and December 2022. Medical records were the secondary source of information. Descriptive and inferential statistics were used. The information was summarized in tables and graphics. Results: 90.6% were over 60 years old and more than half were male (54.5%). Most patients presented various associated symptoms. Personality and orientation disorders were found in 75.3%, while memory disorders were found in 72.7%. Conclusions: The clinical worsening after hospital admission was accentuated in those patients without schooling, single, unemployed, with cerebrovascular diseases and presence of dysfunctional families. Anemic patients or patients with signs of focal cortical irritation in the frontoparietal region with secondary generalization mostly presented clinical worsening.

Rational drug repurposing for alzheimer's treatment using in-silico ligand and structure-based approaches

Abstract Alzheimer's disease is a devastating neurodegenerative disorder characterized by memory loss and cognitive decline. New AD treatments are essential, and drug repositioning is a promising approach. In this study, we combined ligand-based and structure-based approaches to identify potential candidates among FDA-approved drugs for AD treatment. We used the human acetylcholinesterase receptor structure (PDB ID: 4EY7) and applied Rapid Overlay of Chemical Structures and Swiss Similarity for ligand-based screening.Computational shape-based screening revealed 20 out of 760 FDA approved drugs with promising structural similarity to Donepezil, an AD treatment AChE inhibitor and query molecule. The screened hits were further analyzed using docking analysis with Autodock Vina and Schrodinger glide. Predicted binding affinities of hits to AChE receptor guided prioritization of potential drug candidates. Doxazosin, Oxypertine, Cyclopenthiazide, Mestranol, and Terazosin exhibited favorable properties in shape similarity, docking energy, and molecular dynamics stability.Molecular dynamics simulations confirmed the stability of the complexes over 100 ns. Binding free energy analysis using MM-GBSA indicated favourable binding energies for the selected drugs. ADME, formulation studies offered insights into therapeutic applications and predicted toxicity.This comprehensive computational approach identified potential FDA-approved drugs (especially Doxazosin) as candidates for repurposing in AD treatment, warranting further investigation and clinical assessment.

Brain insulin resistance and Alzheimer's disease: a systematic review / Resistência insulínica cerebral e a doença de Alzheimer: uma revisão sistemática

ABSTRACT. The disability of cells to react to insulin, causing glucose intolerance and hyperglycemia, is referred to as insulin resistance. This clinical condition, which has been well-researched in organs such as adipose tissue, muscle, and liver, has been linked to neurodegenerative diseases like Alzheimer's disease (AD) when it occurs in the brain. Objective: The authors aimed to gather data from the current literature on brain insulin resistance (BIR) and its likely repercussions on neurodegenerative disorders, more specifically AD, through a systematic review. Methods: A comprehensive search was conducted in multiple medical databases, including the Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline), and PubMed®, employing the descriptors: "insulin resistance", "brain insulin resistance", "Alzheimer's disease", "neurodegeneration", and "cognition". The authors focused their search on English-language studies published between 2000 and 2023 that investigated the influence of BIR on neurodegenerative disorders or offered insights into BIR's underlying mechanisms. Seventeen studies that met the inclusion criteria were selected. Results: The results indicate that BIR is a phenomenon observed in a variety of neurodegenerative disorders, including AD. Studies suggest that impaired glucose utilization and uptake, reduced adenosine triphosphate (ATP) production, and synaptic plasticity changes caused by BIR are linked to cognitive problems. However, conflicting results were observed regarding the association between AD and BIR, with some studies suggesting no association. Conclusion: Based on the evaluated studies, it can be concluded that the association between AD and BIR remains inconclusive, and additional research is needed to elucidate this relationship.

RESUMO. A incapacidade das células de reagir à insulina, ocasionando intolerância à glicose e hiperglicemia, é chamada de resistência à insulina. Essa condição clínica, que tem sido bem pesquisada em órgãos como tecido adiposo, músculo e fígado, tem sido associada às doenças neurodegenerativas como a doença de Alzheimer (DA) quando ocorre no cérebro. Objetivo: O objetivo dos autores foi reunir os dados da literatura atual sobre a resistência insulínica cerebral (RIC) e sua provável repercussão em doenças neurodegenerativas, mais especificamente na DA, por meio de uma revisão sistemática da literatura. Métodos: Foi realizada uma pesquisa abrangente em vários bancos de dados médicos, incluindo o Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline) e PubMed, empregando os descritores: "resistência à insulina", "resistência insulínica cerebral", "doença de Alzheimer", "neurodegeneração" e "cognição". Os autores concentraram sua busca em estudos no idioma inglês publicados entre 2000 e 2023 que investigaram a influência da RIC em distúrbios neurodegenerativos ou ofereceram insights sobre os mecanismos subjacentes da RIC. Dezessete estudos que atenderam aos critérios de inclusão foram selecionados. Resultados: Os resultados demonstram que a RIC é um fenômeno observado em uma variedade de doenças neurodegenerativas, incluindo a DA. Estudos sugerem que a utilização e captação prejudicadas de glicose, a produção reduzida de trifosfato de adenosina (ATP) e as alterações na plasticidade sinápticas causadas pela RIC estão ligadas a problemas cognitivos. No entanto, foram observados resultados conflitantes com relação à associação entre DA e RIC, com alguns estudos sugerindo nenhuma associação. Conclusão: Com base nos estudos avaliados, pode-se concluir que a associação entre DA e RIC ainda é inconclusiva, e pesquisas adicionais são necessárias para elucidar essa relação.

Chemical Components of Traditional Chinese Medicine in Treating Alzheimer's Disease and Its Mechanism： A Review / 中国实验方剂学杂志

Alzheimer's disease （AD） is one of the most common diseases in the elderly population. Its etiology involves multiple pathogenic factors and pathological links such as abnormal deposition of β amyloid protein （Aβ）， hyperphosphorylation of Tau protein， abnormalities of the cholinergic system， oxidative stress， and inflammatory response. However， its specific pathogenesis has not been clarified， and no specific therapeutic drugs have been found. In recent years， more and more studies have paid attention to the potential of chemical components of traditional Chinese medicine （TCM） in the treatment of AD. However， the diversity and complexity of the chemical components of TCM may have a positive impact on multiple pathological links of AD. Researchers have isolated many active components from TCMs， and the effects of treating AD have been confirmed by modern pharmacological studies. Through literature analysis， this article found that the main chemical components of TCM with anti-AD effects were saponins （31%）， flavonoids （24%）， polysaccharides （20%）， lactones （8%）， alkaloids （7%）， phenols （3%）， and other compounds （7%）. Among them， ginsenoside， notoginsenoside， epimedium flavones， puerarin， baicalein， schisandra polysaccharide， angelica polysaccharide， ganoderma lucidum polysaccharide， pachyman， huperzine A， berberine， andrographolide， curcumin， emodin， and gastrodin have been extensively studied in terms of their anti-AD effects， and their mechanisms of pharmacological action have been involved in many aspects of AD pathogenesis. This article reviews the anti-AD activities and possible mechanisms of chemical components of TCM， so as to provide a reference for the development of new drugs for the prevention and treatment of AD.

The improving effect and mechanisms of Anshen Dingzhi Prescription on Alzheimer's disease-like behavior induced by D-galactose combined with AβO in mice / 药学学报

The purpose of this study was to explore the improving effect of Anshen Dingzhi Prescription (ADP) on Alzheimer's disease (AD)-like behavior in mice and its mechanisms. The main chemical components of ADP were identified by ultra performance liquid chromatography-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The AD-like mouse model was induced by D-galactose (D-gal) combined with Aβ1-42 oligomer (AβO). The effect of ADP on AD-like behavior in mice was assessed using various behavioral experiments; pathomorphological changes in mouse hippocampal tissue were observed by Nissl staining and transmission electron microscopy; ELISA was used in the assessment of oxidative stress factors and inflammation-related factor levels; Western blot was performed to detect the expression of Aβ, Tau and glial fibrillary acidic protein (GFAP) proteins. The active components of ADP were screened according to TCMSP and HERB database, and the action targets of active components were predicted by Swiss Target Prediction platform. In addition, the targets of AD were predicted through DisGeNET database. Further, GO and KEGG enrichment analysis of common targets was carried out by Metascape database. Combined with the results of GO and KEGG analysis, in vivo experiments were carried out to explore the potential mechanism of ADP improving AD-like behavior in mice from the PI3K/Akt, calcium signal pathway and synaptic function. Finally, the core components of ADP were molecularly docked to the validated targets using Autodock Vina. Animal experiments were approved by the Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2021080). The results showed that the five chemical components, including ginsenoside Rg1, ginsenoside Rb1, tenuifolin, poricoic acid B and α-asarone were found in the ADP. ADP significantly improved the anxiety-like behavior and memory impairment, protected hippocampal neurons, decreased the levels of oxidative stress and inflammation, and inhibited the expression of Aβ and p-Tau induced by D-galactose combined with AβO in mice. The results of network pharmacology suggested that PI3K/Akt, calcium signal pathway and cell components related to postsynaptic membrane might be the key factors for ADP to improve AD. Animal experiments revealed that ADP up-regulated N-methyl-D-aspartate receptor 2A (GluN2A), postsynaptic density protein 95 (PSD95), calpain-1, phosphorylated protein kinase B (p-Akt), phosphorylated cAMP response element binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) expression and inhibited p-GluN2B and calpain-2 expression in the hippocampus of AD-like mice. The molecular docking results demonstrated that the core components of ADP, such as panaxacol, dehydroeburicoic acid, deoxyharringtonine, etc. had a high binding ability with the validated targets GRIN2A, GRIN2B, PSD95, etc. In summary, our results indicate ADP improves AD-like pathological and behavioral changes induced by D-galactose combined with AβO in mice, and the mechanism might be related to the NMDAR/calpain axis and Akt/CREB/BDNF pathway.

Protective Effect of Liuwei Dihuangwan on Mitochondrial Damage in AD Model of Caenorhabditis Elegans / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan （LW） on mitochondrial damage in the Alzheimer's disease （AD） model of Caenorhabditis elegans （C. elegans）. MethodC. elegans transfected with human β-amyloid protein （Aβ） 1-42 gene was used as an AD model. The rats were divided into blank group， model group， metformin group （50 mmol·L-1）， and low， medium， and high dose （1.04， 2.08， 4.16 g·kg-1） LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine （5-HT） in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate （ATP） kit， and mitochondrial membrane potential was detected by the JC-1 method. In addition， the mRNA expression of Aβ expression gene （Amy-1）， superoxide dismutase-1 （SOD-1）， mitochondrial transcription factor A homologous gene-5 （HMG-5）， mitochondrial power-associated protein 1 （DRP1）， and mitochondrial mitoprotein 1 （FIS1） was detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT （P<0.05） and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group， in the model group， the mRNA expression of Aβ protein and Amy-1 increased （P<0.01）， and the mRNA expression of SOD-1 and HMG-5 decreased （P<0.01）. The mRNA expression of DRP1 and FIS1 increased （P<0.01）， and the level of mitochondrial membrane potential decreased （P<0.05）. The content of ATP decreased （P<0.01）. Compared with the model group， in the positive medicine group and medium and high dose LW groups， the mRNA expression of Aβ protein and Amy-1 decreased （P<0.05，P<0.01）， and the mRNA expression of SOD-1 and HMG-5 increased （P<0.01）. The mRNA expression of DRP1 decreased （P<0.05，P<0.01）， and that of FIS1 decreased （P<0.01）. The level of mitochondrial membrane potential increased （P<0.01）， and the content of ATP increased （P<0.05，P<0.01）. ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria， protect mitochondrial DNA， reduce the fragmentation of mitochondrial division， repair the damaged mitochondria， adjust the mitochondrial membrane potential， restore the level of neuronal ATP， and reduce the neuronal damage caused by Aβ deposition.

Research progress in assisting in the diagnosis of early Alzheimer's disease through eye structure / 国际眼科杂志(Guoji Yanke Zazhi)

Alzheimer's disease(AD)is a common degenerative disease of the central nervous system in which neuropathological changes precede cognitive dysfunction and behavioral impairment. Currently, early diagnosis of AD is based on invasive and expensive testing techniques that are difficult to use widely in the clinical setting. Therefore, there is an urgent need for new markers to detect AD at an early stage. The eye, as an extension of the brain, has been found to show earlier onset of ocular pathologic changes in patients with AD compared to brain pathologic changes, such as retinal structural abnormalities, visual dysfunction, retinal abnormal protein accumulation, choroidal thickness changes, decreased corneal nerve fiber density, deposition of abnormal Aβ proteins in the lens, and pupillary light decreased sensitivity of response, etc. This article reviews the ocular pathologic changes in AD patients in recent years to provide new ideas for the early clinical diagnosis of AD.

Effects of Jiaohong Pills and Its Prescription on Scopolamine-induced Alzheimer's Disease Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

Condiciones de salud bucodental en personas adultas mayores con enfermedad de Alzheimer: Scoping Review

Introducción: El aumento de la longevidad de las personas ha generado en la última etapa de vida la aparición de enfermedades de tipo multifactorial y relacionadas con el estilo de vida, aumentando la prevalencia de patologías mentales y enfermedades orales. Objetivo: Identificar las condiciones de salud oral en personas adultas mayores con enfermedad de Alzheimer. Métodos: Se planteó una revisión de la literatura tipo Scoping Review, determinando una estrategia de búsqueda para tres bases de datos (Pubmed, EbscoHost y LILACS). Fueron incluidos artículos con diseño de corte transversal, cohorte y casos y controles en idioma español, inglés y portugués entre 2011 y 2021. Se realizó la extracción y evaluación del riesgo de sesgo teniendo en cuenta los criterios de elegibilidad. Resultados: Se seleccionaron 32 artículos para revisión de texto completo y síntesis cualitativa de la información. Alemania y Estados Unidos presentan mayor cantidad de publicaciones, el sexo femenino predominó como población de estudio. Se observó menor frecuencia de cepillado, mayor cantidad de ausencias dentales en pacientes con demencia por Alzheimer y consecuentemente un mayor uso de prótesis en dicha población. Conclusiones: Es importante fortalecer la relación sistémico-oral de los adultos mayores mediante un manejo interdisciplinario entre el geriatra y el odontólogo.

Introduction. The increase in the longevity of individuals has led to the emergence of multifactorial diseases related to lifestyle during the later stages of life, thereby increasing the prevalence of mental disorders and oral diseases. Objective: To identify oral health conditions in older adults with Alzheimer's disease. Methods: A Scoping Review literature review was conducted, outlining a search strategy for three databases (Pubmed, EbscoHost, and LILACS). Articles with a cross-sectional, cohort, or case-control design published in Spanish, English, or Portuguese between 2011 and 2021 were included. Extraction and bias risk assessments were performed based on eligibility criteria. Results: Thirty-two articles were selected for full-text review and qualitative synthesis of information. Germany and the United States had the highest number of publications, with females predominating as the study population. A lower frequency of brushing, a higher number of missing teeth in Alzheimer's patients, and consequently higher use of prosthetics were observed in this population. Conclusions: It is essential to strengthening the systemic-oral relationship in older adults through interdisciplinary management involving geriatricians and dentists.

Introdução: O aumento da longevidade das pessoas tem gerado na última fase da vida o aparecimento de doenças multifatoriais e relacionadas ao estilo de vida, aumentando a prevalência de patologias mentais e doenças bucais. Objetivo: identificar as condições de saúde bucal em idosos com doença de Alzheimer. Métodos: foi realizada uma revisão de escopo da literatura, determinando uma estratégia de busca em três bancos de dados (Pubmed, EbscoHost e LILACS). Foram incluídos artigos com desenho transversal, de coorte e de caso-controle em espanhol, inglês e português entre 2011 e 2021. A extração e a avaliação do risco de viés foram realizadas levando-se em conta os critérios de elegibilidade. Resultados: Trinta e dois artigos foram selecionados para revisão do texto completo e síntese qualitativa das informações. A Alemanha e os Estados Unidos tiveram o maior número de publicações, e a população do estudo era predominantemente feminina. Observou-se menor frequência de escovação, maior número de ausencias odontológicas em pacientes com demência de Alzheimer e, consequentemente, maior uso de dentaduras nessa população. Conclusões: É importante fortalecer a relação sistêmico-oral dos idosos por meio do gerenciamento interdisciplinar entre o geriatra e o dentista.

Behavioral or neuropsychiatric symptoms of Alzheimer's disease: from psychopathology to pharmacological management / Sintomas comportamentais ou neuropsiquiátricos da doença de Alzheimer: psicopatologia e abordagem terapêutica

Abstract Neuropsychiatric or behavioral symptoms of dementia encompass a series of disorders, such as anxiety, depression, apathy, psychosis, and agitation, all commonly present in individuals living with dementia. While they are not required for the diagnosis of Alzheimer's disease (AD), they are ubiquitously present in all stages of the disease, contributing to negative clinical outcomes, including cognitive decline, functional disability, and caregiver burden. Neuropsychiatric symptoms have been conceptualized not only as risk factors but as clinical markers of decline along the AD spectrum. The concept of "mild behavioral impairment", the behavioral correlate of mild cognitive impairment, has been proposed within this framework. The first steps in the management of behavioral symptoms in AD involve defining the target and investigating potential causes and/or aggravating factors. Once these factors are addressed, non-pharmacological approaches are preferred as first-line interventions. Following the optimization of anticholinesterase treatments, specific pharmacological approaches (e.g., antidepressants, antipsychotics) can be considered weighing potential side effects.

Resumo Sintomas neuropsiquiátricos ou comportamentais de demência envolvem uma série de condições, como ansiedade, depressão, apatia, psicose e agitação, frequentemente observadas em indivíduos com demência. Embora esses sintomas não sejam necessários para o diagnóstico da doença de Alzheimer, estão presentes em todas as fases ou estágios da doença, contribuindo negativamente para o declínio cognitivo, comprometimento funcional e sobrecarga do cuidador. Os sintomas neuropsiquiátricos têm sido conceituados não apenas como fatores de risco, mas também como marcadores clínicos de progressão da doença de Alzheimer. O construto "comprometimento comportamental leve", correlato comportamental do comprometimento cognitive leve, tem sido proposto nesse contexto. Os primeiros passos na abordagem dos sintomas comportamentais da doença de Alzheimer envolvem definir os alvos-terapêuticos e investigar potenciais causas ou fatores agravantes. Após intervir nesses fatores, abordagens não farmacológicas constituem a primeira linha de intervenção. Depois da otimização do tratamento anticolinesterásico, terapias farmacológicas específicas (por exemplo, antidepressivos, antipsicóticos) podem ser consideradas, levando-se em conta potencias efeitos colaterais.

The past, present and future of Alzheimer's disease - part 1: the past / O passado, presente e futuro da doença de Alzheimer - parte 1: o passado

Abstract Background Alzheimer's disease (AD) was described in 1907, and since then it changed from a relatively rare condition to one of the most prevalent diseases. Objective To describe the evolution of the notions of dementias and AD, and to investigate the reasons for the increase in scientific interest in AD. Methods A historical analysis was carried out on knowledge about dementia, the site of mental activity, the relationships between brain diseases and mental activity, and on the advances in research about AD, since its discovery until the publication of the amyloid cascade hypothesis in 1992. A search was carried out in the National Library of Medicine (PubMed) for scientific articles that included the terms dementia or AD over 50 years, from 1972 to 2021. Results The scientific research on AD increased from 615 papers with the term AD in the first decade (1972-1981), to 100,028 papers in the last decade (2012-2021): an increase of 162.6 times whereas publications with the term dementia increased 28.6 times in the same period. In the 1960s and 1970s, a consensus was reached that AD is responsible for the majority of cases of dementia previously known as senile dementia. In the 1980s, beta-amyloid peptide was identified in the core of the senile plaque, hyperphosphorylated tau protein was found in neurofibrillary tangles, and a mutation was discovered in a hereditary form of AD. Conclusion The expansion of the concept of AD to include senile dementia, and the discoveries that occurred in the 1980s greatly expanded research in AD.

Resumo Antecedentes A doença de Alzheimer (DA) foi descrita em 1907 e, desde então, deixou de ser relativamente rara para se tornar uma das doenças mais prevalentes. Objetivo Descrever a evolução das noções sobre demências e DA e investigar as razões do aumento do interesse científico pela DA. Métodos Foi realizada uma análise histórica dos conhecimentos sobre demência, o local da atividade mental, as relações entre doenças cerebrais e a atividade mental, e sobre os avanços na pesquisa sobre a DA, desde a sua descoberta até a publicação da hipótese da cascata amiloide em 1992. Foi realizada uma busca na Biblioteca Nacional de Medicina dos Estados Unidos da América (PubMed) por artigos científicos que incluíssem os termos demência ou DA nos 50 anos, de 1972 a 2021. Resultados A pesquisa científica sobre DA aumentou de 615 artigos com o termo doença de Alzheimer na primeira década (1972-1981), para 100.028 artigos na última década (2012-2021): um aumento de 162,6 vezes enquanto as publicações com o termo demência aumentaram 28,6 vezes no mesmo período. Nas décadas de 1960 e 1970, chegou-se a um consenso de que a DA é responsável pela maioria dos casos de demência, anteriormente conhecida como demência senil. Na década de 1980, o peptídeo beta-amiloide foi identificado no núcleo da placa senil, a proteína tau hiperfosforilada foi encontrada em emaranhados neurofibrilares e uma mutação foi descoberta em uma forma hereditária de DA. Conclusão A expansão do conceito de DA para incluir a demência senil e as descobertas ocorridas na década de 1980 ampliaram enormemente a pesquisa em DA.

Correlación entre escalas visuales de atrofia entorrinal y temporomesial con volumetría hipocampal / Correlation between visual scales of entorhinal and temporomesial atrophy with hippocampal volumetry

Resumen Objetivo: En pacientes con enfermedad de Alzheimer (EA) se han descrito cambios neuropatológicos tempranos en la corteza entorrinal, que anteceden el compromiso temporomesial. La evaluación de la atrofia hipocampal mediante escalas visuales y volumetría son herramientas útiles en la valoración de pacientes con deterioro cognitivo. Nuestro objetivo es establecer la correlación entre la evaluación visual de la atrofia de la corteza entorrinal (ACE), la atrofia temporomesial (ATM) y el volumen hipocampal. Material y métodos: Estudio retrospectivo de corte transversal. Se incluyeron pacientes con queja cognitiva y resonancia magnética (RM) cerebral. Se utilizaron escalas visuales de ACE y ATM. Se midió el volumen hipocampal mediante el software volBrain 1.0. Resultados: Se incluyeron 48 pacientes, 31 eran mujeres (64,6%). Mediana de edad: 76,5 (RIQ: 69-83). La correlación entre las escalas visuales ACE y la ATM del lado derecho fue de 0,67 p < 0,0001) y del lado izquierdo de 0,69 (p < 0,0001). Encontramos correlación negativa moderada entre la ACE y el volumen hipocampal, del lado derecho fue de –0,59 (p < 0,0001) y del lado izquierdo de –0,42 (p = 0,003). Conclusión: La escala de ACE muestra moderada correlación con la escala de ATM y con el volumen hipocampal. Su uso podría aportar información valiosa para valoración de trastornos cognitivos.

Abstract Objective: In patients with Alzheimer’s disease (AD), early neuropathological changes in the entorhinal cortex have been described, which precede temporomesial involvement. The evaluation of hippocampal atrophy using visual scales and volumetry are useful tools in the assessment of patients with cognitive impairment. Our objective is to establish the correlation between the visual evaluations of entorhinal cortex atrophy (ECA), temporomesial atrophy (TMA), and hippocampal volume. Material and methods: Retrospective cross-sectional study. Patients with cognitive complaint and brain magnetic resonance imaging (MRI) were included. ACE and TMA visual scales were used. Hippocampal volume was measured using the volBrain 1.0 software. Results: Forty-eight patients were included, 31 were women (64.6%). Median age was 76.5 (IQR: 69-83). The correlation between ECA and TMA on the right side was 0.67 (p < 0.0001) and on the left side was 0.69 (p < 0.0001). We found a negative moderate correlation between ECA and hippocampal volume, on the right side it was –0.59 (p < 0.0001) and on the left side it was –0.42 (p = 0.003). Conclusion: The ECA scale shows high correlation with the TMA scale and moderate correlation with hippocampal volume. Its use could provide valuable information for the assessment of cognitive disorders.

Is there interest of Mexican adults in being prepared should they develop Alzheimer's or other dementia? / ¿Existe interés en adultos mexicanos de preparase en caso de llegar a padecer Alzheimer u otra demencia?

Abstract Introduction Alzheimer's disease, as well as other dementias, cause a progressive deterioration of cognitive functions, preventing patients from making decisions and having control over themselves in an advanced stage of the disease. Objective To explore some expectations, wishes and preferences in a sample of mature adults should they develop Alzheimer or other dementia. Method We surveyed 368 mature Mexican adults without dementia using a large survey created by the authors and used in a previous study; data were collected in some public places where mature people were invited to participate. The survey was completed from July 2019 to August 2020. Results Although most participants had considered they might suffer from dementia in the future, less than half had communicated their wishes to their relatives about future medical treatments in case they could no longer decide for themselves; very few had prepared a written advance directive. Most participants agreed that patients should know their initial diagnosis, mainly to be able to prepare themselves. The main reason given by those who would prefer to hide the diagnosis was to avoid suffering. Discussion and conclusion Our results highlight the need for health professionals to promote discussion with people about the possibility of suffering from dementia, as well as the importance of making decisions in advance, and letting their relatives know about them.

Resumen Introducción La enfermedad de Alzheimer, así como las otras demencias, causan un deterioro progresivo de las funciones cognitivas, evitando que en una etapa avanzada de la enfermedad los pacientes puedan tomar decisiones y tener control sobre sí mismos. Objetivo Explorar algunas expectativas, deseos y preferencias en una muestra de adultos maduros en caso de que llegaran a desarrollar Alzheimer u otra demencia. Método Encuestamos a 368 adultos mexicanos maduros sin demencia usando una encuesta creada por los autores y utilizada en un estudio anterior; los datos se recopilaron en algunos lugares públicos donde se invitó a las personas a participar. La encuesta se aplicó de julio de 2019 a agosto de 2020. Resultados Aunque la mayoría de los participantes había considerado que podría sufrir demencia en el futuro, menos de la mitad había comunicado sus deseos a sus familiares sobre futuros tratamientos médicos en caso de que ya no pudieran decidir por sí mismos; muy pocos habían preparado una voluntad anticipada por escrito. La mayoría de los participantes estuvo de acuerdo en que los pacientes deben conocer su diagnóstico inicial, principalmente para poder prepararse. La principal razón aducida por quienes preferirían ocultar el diagnóstico fue el deseo de evitar sufrimiento. Discusión y conclusión Nuestros resultados destacan la necesidad de que el personal de salud promueva la discusión con las personas sobre la posibilidad de padecer demencia, así como la importancia de tomar decisiones por anticipado e informar de ellas a sus familiares.

Acousto-optic stimuli to promote coherent 40-Hz frequency entrainment effect / Estímulos acústico-ópticos para promover efeito de arrastamento de frequência coerente de 40 Hz

Abstract Background Research has shown that a fundamental frequency of 40 Hz in continuous neural oscillation is indicative of normal brain activity; in Alzheimer disease (AD) patients, these oscillations either disappear or are significantly interrupted. Research has also indicated that the degenerative impacts of AD in mice were mitigated by the synchronization of 40-Hz acousto-optic stimulation (AOS). Objective To examine the impact of employing a 40-Hz AOS intervention on the induction of a substantial 40-Hz frequency entrainment and improvement in working memory performance among a sample of young individuals in good health. We conduct an analysis of event-related potentials (ERPs) derived from electroencephalogram (EEG) data following the presentation of AOS. Methods We recruited 20 healthy volunteers (median age: 25 years; 8 female subjects). Following the administration of various stimuli, including no stimuli, 40-Hz AOS, pink noise, and 40Hz acoustic stimuli (AS), the participants were required to complete a working memory task. A total of 62 electrodes were used to record EEG data, which was subsequently analyzed to investigate the impact of AOS on the activity of working memory. We also aimed to determine if AOS lead to a more pronounced 40-Hz frequency entrainment. Results Following the administration of AOS, a notable enhancement in the 40-Hz power of pertinent cerebral areas was observed, accompanied by a substantial improvement in the performance of the subjects on working memory tests subsequent to the stimulation. Conclusion The findings unequivocally establish the efficacy of using AOS to enhance the 40-Hz power and working memory.

Resumo Antecedentes A pesquisa mostrou que uma frequência fundamental de 40 Hz em oscilação neural contínua é indicativa de atividade cerebral normal. Em pacientes com doença de Alzheimer (DA), essas oscilações desaparecem ou são significativamente interrompidas. A pesquisa também indicou que os impactos degenerativos da DA em camundongos foram mitigados pela sincronização da estimulação acústico-óptica (EAO) de 40 Hz. Objetivo Examinar o impacto do emprego de uma intervenção EAO de 40 Hz na indução de um arrastamento substancial de frequência de 40 Hz e na melhoria do desempenho da memória de trabalho entre uma amostra de jovens com boa saúde. Conduzimos uma análise de potenciais relacionados a eventos (PREs) derivados de dados de eletroencefalograma (EEG) após a apresentação de EAO. Métodos Recrutamos 20 voluntários saudáveis (idade média: 25 anos; 8 mulheres). Após a administração de vários estímulos, incluindo nenhum estímulo, EAO de 40 Hz, ruído rosa e estímulos acústicos (EA) de 40 Hz, os participantes foram obrigados a completar uma tarefa de memória de trabalho. Um total de 62 eletrodos foram utilizados para registrar dados de EEG, que foram posteriormente analisados. para investigar o impacto do AOS na atividade da memória de trabalho. Também pretendemos determinar se o AOS leva a um arrastamento de frequência de 40 Hz mais pronunciado. Resultados Após a administração de AOS, foi observado um aumento notável na potência de 40 Hz de áreas cerebrais pertinentes, acompanhado por uma melhoria substancial no desempenho dos sujeitos em testes de memória de trabalho subsequentes à estimulação. Conclusão Os resultados estabelecem inequivocamente a eficácia do uso do AOS para melhorar a potência de 40 Hz e a memória de trabalho.

Traducción al español, retraducción y validación de contenido de la escala Quality of Life in Alzheimer's Disease en pacientes con demencia Alzheimer / Spanish translation, retranslation, and content validation of the Quality of Life in Alzheimer's Disease scale in patients with Alzheimer's dementia

Introducción Se estima que para el año 2050 los mayores de 60 años corresponderán al 22% de la población mundial y con ello aumente la incidencia y prevalencia de enfermedad de Alzheimer. Uno de los pilares del tratamiento de esta condición es mejorar la calidad de vida, en este sentido surgen herramientas como la Quality of Life in Alzheimer's Disease Scale que permite medir calidad de vida en pacientes y sus cuidadores. Objetivo Realizar la traducción al español chileno y validación de contenido de la Quality of Life in Alzheimer's Disease Scale en pacientes con demencia por Alzheimer del Hospital Guillermo Grant Benavente de Concepción, Chile. Métodos Se llevó a cabo la traducción, retraducción y validez de contenido por juicio experto, utilizando el análisis Lawshe, pre-test y validación semántica usando la estrategia de respondent debriefing. Resultados Las versiones traducidas y retraducidas fueron comparadas entre ellas y con la versión original. Lawshe indica que una razón de validez de contenido de 0,49 es adecuado para considerar aceptable el ítem cuando en el proceso de validación de contenido han participado 15 expertos como en este estudio. El análisis arrojó una razón de validez de contenido mayor a 0,49 en 11 de los 13 ítems de la escala. De estos, ocho obtuvieron un valor superior a 0,8 y tres entre 0,49 y 0,79. En la validación semántica mediante la estrategia de se aplicó la escala a cinco personas con enfermedad de Alzheimer y a sus respectivos cuidadores. Con los datos obtenidos, se generaron modificaciones en aquellos ítems que obtuvieron una razón de validez de contenido menor a 0,49. Conclusión La versión obtenida en español de la resulta ser válida desde el punto de vista de su contenido y equivalente a su versión original.

Introduction It is estimated that by the year 2050, persons over 60 will account for 22% of the world population. Consequently, the incidence and prevalence of Alzheimer's disease will increase correspondingly. One of the pillars of the treatment of this condition is to improve the quality of life. In this sense, questionnaires such as the Quality of Life in Alzheimer's Disease allow us to measure the quality of life in patients and caregivers. Objective To translate into Chilean Spanish and carry out the content validation of the Quality of Life in Alzheimer's Disease scale in patients with Alzheimer's dementia at the Guillermo Grant Benavente Hospital in Concepción, Chile. Methods Translation, back-translation and content validity were carried out by expert judgment, using Lawshe analysis, pre-test and semantic validation using the respondent debriefing strategy. Results The translated and retranslated versions were compared with each other and with the original version. Lawshe indicates that a Content Validity Ratio equal 0.49 is adequate to consider the item valid when 15 experts participated in the content validation process, as in our study. The analysis yielded a content validity ratio greater than 0.49 in 11 of the 13 items on the scale. Of these, 8 obtained a value greater than 0.8 and 3 between 0.49 and 0.79. In semantic validation using the respondent debriefing strategy, the scale was applied to five people with Alzheimer's and their respective caregivers. With the data obtained, modifications were generated in those items that obtained a content validity ratio of less than 0.49. Conclusions The version obtained in Spanish of the Quality of Life in Alzheimer's Disease scale is valid from the point of view of its content and equivalent to its original version.

Composición química y aplicaciones clínicas del aceite de oliva extra virgen

La composición química del aceite de oliva extra virgen (AOEV) se compone principalmente de triglicéridos, ácidos grasos insaturados como ácido oleico, ácido linoleico y el α-linolénico. También se destacan compuestos fenólicos de tres clases químicas: simples, secoiridoides y lignanos. En la presente revisión se analizó el consumo del AOEV en enfermedades crónicas, ciertos tipos de cáncer y en enfermedades neurodegenerativas. La evidencia muestra que el consumo de entre 8 y 40 g de AOEV diario tiene efectos protectores en enfermedades cardiovasculares, puede evitar la aparición de diabetes tipo 2 y aumentar los niveles de colesterol HDL. Respecto al cáncer, entre los efectos evaluados se destacan los encontrados a partir de los compuestos fenólicos hidroxitirosol (HT) y oleocantal, los que han demostrado un efecto protector en algunos tipos de cáncer como cáncer de piel y de mama. En las enfermedades neurodegenerativas, se observó que el consumo diario de 50 g de AOEV, tiene un efecto inhibidor en la degeneración neuronal atribuido a sus compuestos fenólicos como oleuropeina e HT. Investigaciones a futuro debieran enfocarse en determinar los efectos a largo plazo del consumo de AOEV en las diferentes enfermedades analizadas, para así poder ir estableciendo la "dosis" de AOEV que permita obtener resultados protectores sobre la salud. Además de explorar los efectos de las diferentes variedades de aceitunas (con sus componentes bioactivos particulares) con el fin de establecer los efectos en la salud y enfermedad asociados a variedades específicas.

The chemical composition of extra virgin olive oil (EVOO) is mainly composed of triglycerides, unsaturated fatty acids such as oleic acid, linoleic acid, and α-linolenic acid. Phenolic compounds of three chemical classes are also relevant, such as simple, secoiridoids, and lignans. Here, we review the association between EVOO consumption and chronic diseases, certain types of cancer, and neurodegenerative diseases. Evidence shows that consuming between 8 and 40 g of EVOO / day has protective effects on cardiovascular diseases, can prevent the onset of type 2 diabetes, and increases HDL cholesterol levels. Regarding cancer, phenolic compounds hydroxytyrosol (HT) and oleocanthal have protective effects on some types of cancer, such as skin and breast cancer. Regarding neurodegenerative diseases, daily consumption of phenolic compounds such as oleuperin and hydroxytyrosol and 50 g of EVOO has an inhibitory effect on neuronal degeneration and a protective effect on neuroprotective capacity. Future research should focus on determining the long-term impact of EVOO consumption on different diseases to establish the "dose" of EVOO that will allow health-protective results. It is also necessary to establish the effects of the specific olives (with their particular bioactive components) to establish the different impacts on health and disease associated with olives varieties.

Role of Aluminium in Alzheimer’s disease: Ultrastructural Study in Rat Hippocampus

Background: Exposure to high levels of aluminium (Al) leads to neurotoxicity. Hippocampus is one of the preferred sites of aluminium accumulation. Nevertheless, the role of Al in Alzheimer’s disease (AD) remains controversial and there is little proof directly interlinking Al to AD. Aims: The present study was undertaken to find out the occurrence of AD pathogenesis in Hippocampus under moderate aluminium exposure in rats. Materials and Methods: Adult rats were divided into control (C) and aluminium treated (E) groups having eight animal each. The rats in group E were exposed to aluminium 4.2 mg/kg body weight for three months with due approval from Institute Animal Ethics Committee. The hippocampus was processed for histopathological and electron microscopy observation. Results: Moderate Al intake produces significant reduction in the count of Pyramidal cells in hippocampus identified by shrunken cells as well as pyknosis in cell bodies. The differences between the cell numbers in all groups were found to be statistically significant (P < 0.05). Cornu Ammonis (CA) exhibited significantly reduced nissl bodies with a marked reduction in neuronal cell loss. Neurofibrillary tangle and plaques were not seen in the given dose of Al exposure. Electron microscopy from experimental group showed that the majority of neurons were disintegrating, the nuclear membrane has ruptured, and nucleoli appeared significantly distorted. The chromatin condensed and the mitochondria had disintegrated. Many vacuoles and lipofuscin sediment in cytoplasm, as compared to the control group noted. Conclusion: Present data demonstrated that moderate chronic aluminium exposure 4.2mg/kg body weight induced neurodegeneration in hippocampus but not significant for Alzheimer’s disease pathogenesis.