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.

Diffuse neurofibrillary tangles with calcification / 中华老年医学杂志

Diffuse neurofibrillary tangles with calcification(DNTC)is a rare neurodegenerative disease and belongs to the category of tauopathies.The main characteristics of DNTC include presenile dementia, symmetrical bilateral calcification in the basal ganglia and cerebral dentate nuclei, and bilateral atrophy of the temporal lobes.At present, the majority of reported cases with DNTC were from Japan, with only a few cases from other countries.Although DNTC is a pathological diagnosis based on autopsy, ante-mortem diagnosis for DNTC can be achieved based on clinical features and presentation of brain tau protein shown on positron emission computed tomography.The clinical characteristics, pathological changes and diagnosis criteria of DNTC are reviewed in this paper.

Relationships between ¹⁸F-THK5351 Retention and Language Functions in Primary Progressive Aphasia

BACKGROUND AND PURPOSE: There are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [¹⁸F]-THK5351 retention across all three subtypes and determine the topography of [¹⁸F]-THK5351 retention correlated with each neurolinguistic score. METHODS: We enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [¹⁸F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [¹⁸F]-THK5351 retention. RESULTS: The nfvPPA patients exhibited higher [¹⁸F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [¹⁸F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [¹⁸F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [¹⁸F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [¹⁸F]-THK5351 retention in the left temporal cortices. Repetition was associated with [¹⁸F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices. CONCLUSIONS: The pattern of [¹⁸F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.

Effect of Wuzang Wenyang Huayu Decoction on Neurofibrillary Tangles by Inhibiting Cyclin-dependent Kinase-5 Over-expression in SAMP8 Mice / 中国实验方剂学杂志

Objective: To explore the mechanism of Wuzang Wenyang Huayu decoction in improving the cognitive competence and the pharmacological mechanism for neurofibrillary tangles related to cyclin-dependent kinase-5(CDK-5).Method: The 10 SAMR1 mice were used as normal group,40 SAMP8 mice were randomly divided into model group,donepezil group (0.4 mg·kg-1·d-1),high and low dose Wuzang Wenyang Huayu decoction groups (5,1.25 g·kg-1·d-1).Drugs were administered by gastric lavage for 4 continuous weeks.Directional navigation and space exploration ability were evaluated with Morris amaze.Real-time PCR was used to measure the mRNA expression of CDK-5 in brain nerve tissues.Western blot was used to detect the protein expression of CDK-5 and phosphorylation of Tau protein.Meanwhile,neurofibrillary tangles in brain tissue were detected with silver staining method.Result: As compared with normal group,both CDK-5 expression and Tau protein phosphorylation in brain nerve tissues were remarkably increased in model group (PPPPPPConclusion: Wuzang Wenyang Huayu decoction can markedly improve the cognitive competence of SAMP8 mice,and the mechanism may be related to its inhibition on CDK-5 over-expression,and down-regulation of Tau protein phosphorylation and neurofibrillary tangles in brain tissue.

Research advances in diffuse neurofibrillary tangles with calcification (Kosaka-Shibayama disease) / 中华神经科杂志

Diffuse neurofibrillary tangles with calcification (DNTC) is a type of presenile dementia. The clinical features are temporal and/or frontal and/or extrapyramidal symptoms. Memory impairment which might be less prominent in early stages of disease becomes evident with progression; The imagings are featured with bilateral basal ganglia and/or cerebellar dentate calcification (Fahr-type calcification) and/or localized atrophy of temporal or temporofrontal lobes; The pathological features are diffuse neurofibrillary tangles without large number of Aß amyloid plaques (characteristic of Alzheimer′s disease) and without Pick body (characteristic of Pick disease), and calcium deposition is similar to Fahr′s disease in sites but minor in degree. Till now, most case reports are from Japan. It is speculated that there are a large number of misdiagnosis in other countries. Criteria for clinical diagnosis of DNTC was proposed by Iwai K(1995), Kosaka H(2001), Ukai K and Kosaka K (2016, 2017) successively, which can facilitate the diagnosis.

Research advances in diffuse neurofibrillary tangles with calcification (Kosaka?Shibayama disease) / 中华神经科杂志

Diffuse neurofibrillary tangles with calcification (DNTC) is a type of presenile dementia. The clinical features are temporal and/or frontal and/or extrapyramidal symptoms. Memory impairment which might be less prominent in early stages of disease becomes evident with progression; The imagings are featured with bilateral basal ganglia and/or cerebellar dentate calcification (Fahr?type calcification) and/or localized atrophy of temporal or temporofrontal lobes; The pathological features are diffuse neurofibrillary tangles without large number of A?amyloid plaques (characteristic of Alzheimer′s disease) and without Pick body (characteristic of Pick disease), and calcium deposition is similar to Fahr′s disease in sites but minor in degree. Till now, most case reports are from Japan. It is speculated that there are a large number of misdiagnosis in other countries. Criteria for clinical diagnosis of DNTC was proposed by Iwai K(1995), Kosaka H(2001), Ukai K and Kosaka K (2016, 2017) successively, which can facilitate the diagnosis.

Research Progress in the Pathogenesis of Alzheimer's Disease / 中华医学杂志(英文版)

<p><b>Objective</b>Alzheimer's disease (AD) is a kind of chronic degenerative disease of the central nervous system, characteristics of cognitive dysfunction, and behavioral disability. The pathological changes include the formation of senile plaques-containing beta-amyloid (Aβ), neurofibrillary tangles (NFTs), loss of neurons, and synapses. So far, the pathogenesis of AD is still unclear. This study was aimed to review the major pathogenesis of AD-related to the published AD studies in recent 20 years.</p><p><b>Data Sources</b>The author retrieved information from the PubMed database up to January 2018, using various search terms and their combinations, including AD, Aβ, NFTs, pathogenesis, and genetic mutation.</p><p><b>Study Selection</b>The author included data from peer-reviewed journals printed in English and Chinese on pathophysiological factors in AD. He organized these informations to explain the possible pathogenesis in AD.</p><p><b>Results</b>There are many amounts of data supporting the view that AD pathogenesis so far there mainly are Aβ toxicity, tau protein, gene mutation, synaptic damages, intermediate neurons and network abnormalities, changes in mitochondrial function, chemokines, etc., Its nosogenesis may be involved in multiple theories and involved in multiple molecular signaling pathways, including Aβ, tau protein, and synaptic anomaly; mutual relationship between the mechanisms urge jointly neuronal degeneration.</p><p><b>Conclusions</b>This review highlights the research advances in the pathogenesis of AD. Future research has needed to fully disclose the association between multiple pathogenesis at the same time to interdict multiple signaling pathways, etc.</p>

¹⁸F-THK5351 PET Imaging in Nonfluent-Agrammatic Variant Primary Progressive Aphasia

BACKGROUND AND PURPOSE: To analyze 18F-THK5351 positron emission tomography (PET) scans of patients with clinically diagnosed nonfluent/agrammatic variant primary progressive aphasia (navPPA). METHODS: Thirty-one participants, including those with Alzheimer's disease (AD, n=13), navPPA (n=3), and those with normal control (NC, n=15) who completed 3 Tesla magnetic resonance imaging, 18F-THK5351 PET scans, and detailed neuropsychological tests, were included. Voxel-based and region of interest (ROI)-based analyses were performed to evaluate retention of 18F-THK5351 in navPPA patients. RESULTS: In ROI-based analysis, patients with navPPA had higher levels of THK retention in the Broca's area, bilateral inferior frontal lobes, bilateral precentral gyri, and bilateral basal ganglia. Patients with navPPA showed higher levels of THK retention in bilateral frontal lobes (mainly left side) compared than NC in voxel-wise analysis. CONCLUSIONS: In our study, THK retention in navPPA patients was mainly distributed at the frontal region which was well correlated with functional-radiological distribution of navPPA. Our results suggest that tau PET imaging could be a supportive tool for diagnosis of navPPA in combination with a clinical history.

Progress on chemokines participating in Alzheimer′s disease / 中国药理学通报

Chemokines play pleiotropic roles in the pathology of Alzheimer′s disease(AD),a chronic inflammatory disease of central nervous system.The neuropathological features of AD include neurofibrillary tangles,amyloid plaques,neuroinflammation,and neuronal synaptic loss.Chemokines are involved in the pathogenesis of AD by activating or regulating inflammatory cells or glial cells,playing dual key roles of the pro-and anti-inflammatory properties in AD.The levels of chemokines in serum,cerebrospinal fluid and brain tissue of AD patients are changed accordingly.This review summarizes the role of chemokines and their receptors in AD in the biological activities and unveils the changing rules,aiming to provide new strategies for clinical treatment of AD.

Vesicle glutamate transporters and Alzheimer’s disease / 国际药学研究杂志

Vesicle glutamate transporter (VGLUT) specifically transfers glutamate into synaptic vesicle, determines the amount of glutamate released into the synaptic cleft, then regulates the efficiency of glutamatergic synaptic transmission. VGLUT plays an important role in the pathogenesis of Alzheimer's diseases (AD). VGLUT is significantly decreased in the brain of AD patients and closely correlated with cognitive dysfunction, beta- amyloid aggregation, tau protein phosphorylation and glutamate excitoxicity. VGLUT, the possible specific biomarker of glutamatergic neuron, has been considered a potential drug target in the treatment of AD and biomarkers in the early diagnosis of AD. There are some advances on chemicals targeting on VGLUT.

The diagnostic value of diffusion tensor imaging for gliomas grading at 3 .0T MRI / 重庆医学

Objective To explore the diagnostic value of axial diffusion tensor imaging(DTI) for gliomas grading at 3 .0T MRI , analyze the characteristics of different grades gliomas of axial DTI in order to improve diagnostic accuracy .Methods A retrospec‐tive analysis was performed involving a group of 37 cases of high grade glioma and 26 cases of low grade glioma confirmed by the pathological results in affiliated hospital of Luzhou medical college ,observation analysis was obtained in axial DTI ,peritumoral neu‐rofibrillary was divided into three types :displacement ,interruption and neurofibrillary tangles(NFT) .Results among the 26 cases of low grade glioma ,there were 18 cases of displacement ;8 cases of interruption ,no NFT ;among the 37 cases of high grade glio‐mas ,there were 9 cases of displacement ,21 cases of interruption ,and 7 cases of NFT (1 case of frontal lobe ,6 cases of temporal lobe);ordinal variables rank sum test in two independent samples between high grade glioma group and low grade glioma showed significant differences(Z= -3 .756 ,P0 .05) ,frontal lobe appeared NFT in 1 case ,accounting for 2 .7% (1/37) ,temporal lobe appeared NFT in 6 cases ,accounting for 16 .2% (6/37) .Conclusion Peritumoral neurofibrillary of the low grade gliomas more performed displacement ,the high grade gliomas show more interrupts and NFT at 3 .0T MRI ,NFT in high grade gliomas is often seen in the temporal and frontal lobe .

Advance in Drug Development for Alzheimer's Disease Targeted Microtuble Associated Protein Tau (review) / 中国康复理论与实践

Alzheimer's disease (AD) is the general neurodegenerative disease in the elderly. Alterations of microtubule associated pro-tein tau are closely related to the onset and progression of AD. The role of tau protein in the development of AD has been a focus in the cur-rent study of AD, with an emphasis on the identification of compounds that inhibit tau protein phosphorylation and aggregate, and accelerate tau protein depolymerization. The current research status of tau protein as target of AD preventive and therapeutic drug was also reviewed.

Advance in Relationship between Tau Protein and Alzheimer's Disease (review) / 中国康复理论与实践

Alzheimer's disease is a common neurodegenerative disease. One of the main pathology is neurofibrillary tangles in neurons, in which principal component is the phosphorylation of tau protein. Previous studies focused on senile plaques and Aβlevels. Recent studies indicated that the development of tau protein closely associated with Alzheimer's disease, especially the abnormal phosphorylation. This pa-per reviewed the relationship between tau protein phosphorylation and Alzheimer's disease based on the perspective of protein kinases and phosphatases.

Establishment of APPswe/PS1 dE9/TAU triple transgenic rat model of alzheimer disease / 中国比较医学杂志

Objective To develop a model that could roundly show the phenotypes of human alzheimer disease (AD), the triple-transgenic rat model harboring APP(Swe), PS1dE9, and TAU transgenes was established in view of the advantage of rat as an important animal model on the research of nerve system .Methods APPswe/PS1dE9/TAU triple transgenic rat AD rats were generated on a SD background by co-injecting rat pronuclei with two human genes driven by the mouse prion promoter:‘Swedish’ mutant human APP (APPsw) and exon 9 mutant human presenilin-1 (PS1dE9) and human microtubule-associated protein tau gene under the control of PDGF promoter .Transgene integration was confirmed by genotyping and expression levels were evaluated by western blot ( WB ) of brain homogenates .The pathological changes were detected by human Abeta, TAU and Phospho-PHF-TAU immunohistochemistry staining (IHC).The behavioral and cognitive changes were evaluated by Morris water maze .Results One transgenic rat lines with high human APP ( Swe ) , PS1dE9, and TAU transgenic expression was selected from three transgenic founders .Compared with the wild type rat , the transgenic rat showed significant learning and memory impairments in the Morris water maze at 6 months of age .The triple transgenic rat manifested hyperphosphorylated tau and obvious aggregation of amyloid -β( Aβ) in the brain cortex and hippocampus.Conclusion APPswe/PS1dE9/TAU triple transgenic rat AD model was established .The triple transgenic AD rat fills a critical need for a next-generation animal model to enable basic and translational AD research .

Advance in Drug Development for Alzheimer's Disease Targeted Microtuble Associated Protein Tau (review) / 中国康复理论与实践

@#Alzheimer's disease (AD) is the general neurodegenerative disease in the elderly. Alterations of microtubule associated protein tau are closely related to the onset and progression of AD. The role of tau protein in the development of AD has been a focus in the current study of AD, with an emphasis on the identification of compounds that inhibit tau protein phosphorylation and aggregate, and accelerate tau protein depolymerization. The current research status of tau protein as target of AD preventive and therapeutic drug was also reviewed.

Estudo da degradação da proteína Tau hiperfosforilada por vias independentes do proteassoma, em modelo experimental de neurodegeneração / Study of hyperphosphorylated Tau protein degradation by proteasome-independent pathways, in an experimental model of neurodegeneration

O desenvolvimento das doenças neurodegenerativas, como a doença de Alzheimer, está associado à presença de agregados proteicos contendo Tau hiperfosforilada (p-Tau). Esta disfunção da Tau leva a prejuízos na homeostase celular. Um mecanismo chave para diminuir e/ou prevenir os danos promovidos pelos agregados contendo Tau seria o estímulo de sua degradação. Neste sentido, a proposta do presente estudo foi analisar a degradação da proteína Tau após aumento da expressão exógena da cochaperona Bag-2, a qual influencia o sistema proteassomal de degradação; bem como avaliar a ativação dos sistemas de degradação, a fim de correlacionar estes sistemas em cultura de células primárias e organotípica do hipocampo de ratos. Os resultados mostraram que a rotenona foi capaz de aumentar os níveis de p-Tau e que a superexpressão de Bag-2, foi eficiente em prevenir e degradar a p-Tau. O mecanismo envolvido neste processo envolve a coordenação dos sistemas proteassomal e lisossomal, já que a Rab7 e a Rab24 (envolvidas na via lisossomal) mostraram-se diminuídas na fase que antecede a agregação proteica, enquanto houve aumento da Rab24 na presença dos agregados proteicos. Com relação ao peptídeo beta amiloide, foi demonstrado tendência de aumento de p-Tau acompanhado de diminuição da atividade proteassomal e lisossomal. O tratamento com PADK (ativador lisossomal) foi capaz de reverter este efeito nestas diferentes condições. A análise da interrelação entre os sistemas mostrou que uma inibição do proteassoma favorece a via lisossomal e que o inverso não se repete. Os resultados sugerem que a modulação das vias de degradação pode ser interessante para o estudo, prevenção e tratamento das doenças neurodegenerativas associadas à agregação de proteínas...

Neurodegenerative diseases, such as Alzheimer's, are associated to protein inclusions containing hyperphosphorylated Tau (p-Tau). It is well established that Tau dysfunction impairs cell homeostasis. A key mechanism to prevent and/or reduce the damage promoted by aggregates of Tau might be its degradation. In view of this, the aims of the present study are to evaluate p- Tau clearance following exogenous expression of Bag-2, which stimulates proteasome; as well as to analyze the activation of both lysosome and proteasome pathways in order to understand the crosstalk between these two systems in primary and organotypic cultures of rat hippocampus. Results showed that rotenone was able of increasing p-Tau that was prevented and degraded by Bag-2 overexpression. Mechanisms involved in this process involve the coordination of cell degradation systems, depending upon aggregation status, since Rab7 and Rab24 (involved in lysosomal pathway) were decreased before protein aggregation, while Rab24 increased in the presence of protein inclusions. Amyloid-beta peptide also increased p-Tau accompanied by decreased proteasome and lysosome activity. PADK (lysosomal activator) treatment reverted the inhibition promoted by amyloidbeta peptide. Inhibition of proteasome leads to activation of lysosome, but lysosome inhibition does not affect proteasome. Overall, results suggest that targeting degradation pathways might be useful to understand, prevent and treat neurodegenerative diseases associated with protein deposits...

Insights into Alzheimer disease pathogenesis from studies in transgenic animal models

Alzheimer disease is the most common cause of dementia among the elderly, accounting for ~60-70 percent of all cases of dementia. The neuropathological hallmarks of Alzheimer disease are senile plaques (mainly containing p-amyloid peptide derived from amyloid precursor protein) and neurofibrillary tangles (containing hyperphosphorylated Tau protein), along with neuronal loss. At present there is no effective treatment for Alzheimer disease. Given the prevalence and poor prognosis of the disease, the development of animal models has been a research priority to understand pathogenic mechanisms and to test therapeutic strategies. Most cases of Alzheimer disease occur sporadically in people over 65 years old, and are not genetically inherited. Roughly 5 percent of patients with Alzheimer disease have familial Alzheimer disease-that is, related to a genetic predisposition, including mutations in the amyloid precursor protein, presenilin 1, and presenilin 2 genes. The discovery of genes for familial Alzheimer disease has allowed transgenic models to be generated through the overexpression of the amyloid precursor protein and/or presenilins harboring one or several mutations found in familial Alzheimer disease. Although none of these models fully replicates the human disease, they have provided valuable insights into disease mechanisms as well as opportunities to test therapeutic approaches. This review describes the main transgenic mouse models of Alzheimer disease which have been adopted in Alzheimer disease research, and discusses the insights into Alzheimer disease pathogenesis from studies in such models. In summary, the Alzheimer disease mouse models have been the key to understanding the roles of soluble b-amyloid oligomers in disease pathogenesis, as well as of the relationship between p-amyloid and Tau pathologies.

Suppression of Autophagy and Activation of Glycogen Synthase Kinase 3beta Facilitate the Aggregate Formation of Tau

Neurofibrillary tangle (NFT) is a characteristic hallmark of Alzheimer's disease. GSK3beta has been reported to play a major role in the NFT formation of tau. Dysfunction of autophagy might facilitate the aggregate formation of tau. The present study examined the role of GSK3beta-mediated phosphorylation of tau species on their autophagic degradation. We transfected wild type tau (T4), caspase-3-cleaved tau at Asp421 (T4C3), or pseudophosphorylated tau at Ser396/Ser404 (T4-2EC) in the presence of active or enzyme-inactive GSK3beta. Trehalose and 3-methyladenine (3-MA) were used to enhance or inhibit autophagic activity, respectively. All tau species showed increased accumulation with 3-MA treatment whereas reduced with trehalose, indicating that tau undergoes autophagic degradation. However, T4C3 and T4-2EC showed abundant formation of oligomers than T4. Active GSK3beta in the presence of 3-MA resulted in significantly increased formation of insoluble tau aggregates. These results indicate that GSK3beta-mediated phosphorylation and compromised autophagic activity significantly contribute to tau aggregation.

Immunohistochemical analysis of β-amyloid and AT8 in late-onset Alzheimer' s disease / 中华神经科杂志

Objective To study the neuropathological characteristics of late-onset Alzheimer' s disease (LOAD) in Chinese people, to ensure correct diagnosis of LOAD.Methods Choosing cerebral cortex of temporal layer of 8 cases of LOAD and 5 cases of age-matched normal control group by autopsy.Histopathologlc diagnosis was established in all these 13 cases.Cerebral cortex were taken from temporal layer in 13-101 hours after death and were fixed with 40 g/L paraformaldehyde, followed by paraffin-embedding and serial sectioning with 6 μm thickness.Brain tissue was analyzed neuropatholically by using immunohistochemical staining for β-amyloid (Aβ) and AT8 on these cases.Positive distribution of temporal layer was observed under light microscope.Results The results of immunohistochemical stainings of Aβ and AT8 were positive in all of LOAD.Aβ immunoreactant located in the cerebral cortex.The diffuse plaques, primitive plaques and burn-out plaques of senile plaques were displayed clearly by immunohistochcmical stainings of Aβ.AT8 immunoreactants showed neurofibrillary tangles, neuropil thread and senile plaques in nerve cell of cerebral cortex in different degree respectively.The positive rate Aβ and AT8 were both 8/8 by semiquantitative analysis in AD group.As the normal aging control group, which was 0 and 1/5 respectively.There was significant difference of the positive rate Aβ and AT8 in two groups(χ2 = 13.000,P=0.001; χ2=9.244,P=0.007).Conclusions Sensitive immunnhistochemical technique was significant to display senile plaques and neurofibrillary tangles.The findings demonstrate that immunohistochemistry staining of Aβ and AT8 can display senile plaques and neurofibrillary tangles clearly.The connection of the 2 different methods might improve diagnose accordance rate of AD.

The characteristics of neurofibrillary tangles in brains of patients with Niemann-Pick disease type C / 中华神经科杂志

Objective To describe the spatial and temporal characteristics of neurofibrillary tangles (NFT) in brains of patients with Niemann-Pick disease type C (NPC). Methods In order to analyze formation of NFT in NPC, the brains collected from 17 patients with NPC aged from 7 months to 55 years old were investigated using antibodies against the protein tau and the specific proteins in mitotic phase. Results Typical NFT could be detected in the parahippocampns of a NPC patient as early as at 4 years old. The number of NFT were increasing along with the time. Gradually, the hippocampus and other regions of the temporal lobes and the frontal lobes would be affected with the time. Immunohistochemically, the NFT formed the shape similar to NFT seen in AD brains, without the presence of senile plagues. Interestingly,mitosis-phase markers appeared in the degenerating NPC neurons prior to hyperphesphorylation of tau and formation of NFT. Conclusions The formation of NFT does not result from aging, for there is no close relation between the presence of senile plagues and the formation of NFT. Ectopic activation of cdc2/cyclinB1 kinase complex might be an early event leading to NFT formation. Antagonist of the kinase complex may potentially slow down the formation of NFT.