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1.
PLoS One ; 17(7): e0271611, 2022.
Article in English | MEDLINE | ID: covidwho-1951558

ABSTRACT

BACKGROUND: Dementia is a major public health priority. Although there is abundant evidence of an association between dementia and poor cardiovascular health, findings have been inconsistent and uncertain in identifying which factors increase dementia risk in those with cardiovascular disease. Indeed, multiple variables including sociodemographic, economic, health, lifestyle and education may indicate who is at higher vs. lower dementia risk and could be used in prediction modelling. Therefore, the aim of this review is to synthesise evidence on the key risk factors for dementia in those with a history of cardiovascular disease. METHODS: This is an overview of reviews protocol, registered on PROSPERO (CRD42021265363). Four electronic databases including MEDLINE, EMBASE, PsycINFO, and the Cochrane Database of Systematic Reviews will be searched. Studies will be included if they are systematic reviews and/or meta-analyses that have investigated the risk of incident dementia (all-cause and subtypes including Alzheimer's disease and vascular dementia) in people with a history of coronary heart disease, heart failure, atrial fibrillation, hypertension, hyperlipidaemia, and vascular stiffness. Study selection will be completed by two independent researchers according to the eligibility criteria, and conflicts resolved by a third reviewer. References will be exported into Covidence for title and abstract sifting, full-text review, and data extraction. Methodological quality will be assessed using the AMSTAR-2 criteria and confidence of evidence will be assessed using the GRADE classification. This overview of reviews will follow PRISMA guidelines. If there is sufficient homogeneity in the data, the results will be pooled, and a meta-analysis conducted to determine the strength of association between each risk factor and incident all-cause dementia and its subtypes for each cardiovascular diagnoses separately. DISCUSSION: We will create a comprehensive summary of the key risk factors linking cardiovascular diseases to risk of incident dementia. This knowledge is essential for informing risk predictive model development as well as the development of risk reduction and prevention strategies.


Subject(s)
Alzheimer Disease , Cardiovascular Diseases , Dementia, Vascular , Alzheimer Disease/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Humans , Meta-Analysis as Topic , Review Literature as Topic , Risk Factors
2.
Nature ; 607(7918): 249-255, 2022 07.
Article in English | MEDLINE | ID: covidwho-1947377

ABSTRACT

Our body has a remarkable ability to remember its past encounters with allergens, pathogens, wounds and irritants, and to react more quickly to the next experience. This accentuated sensitivity also helps us to cope with new threats. Despite maintaining a state of readiness and broadened resistance to subsequent pathogens, memories can also be maladaptive, leading to chronic inflammatory disorders and cancers. With the ever-increasing emergence of new pathogens, allergens and pollutants in our world, the urgency to unravel the molecular underpinnings of these phenomena has risen to new heights. Here we reflect on how the field of inflammatory memory has evolved, since 2007, when researchers realized that non-specific memory is contained in the nucleus and propagated at the epigenetic level. We review the flurry of recent discoveries revealing that memory is not just a privilege of the immune system but also extends to epithelia of the skin, lung, intestine and pancreas, and to neurons. Although still unfolding, epigenetic memories of inflammation have now been linked to possible brain disorders such as Alzheimer disease, and to an elevated risk of cancer. In this Review, we consider the consequences-good and bad-of these epigenetic memories and their implications for human health and disease.


Subject(s)
Adaptation, Physiological , Epigenesis, Genetic , Health , Inflammation , Adaptation, Physiological/genetics , Alzheimer Disease/genetics , Humans , Immunologic Memory , Inflammation/genetics , Neoplasms/genetics
3.
Int J Environ Res Public Health ; 19(13)2022 Jun 30.
Article in English | MEDLINE | ID: covidwho-1934061

ABSTRACT

The literature suggests that leisure walking can play an important role in preventing dementia. The purpose of the present study was to investigate the relationship between leisure walking and the prevalence of Alzheimer's disease (AD) and other dementias among older adults. Using the 2020 Health and Retirement Study (HRS), 4581 responses constituted the sample for the present study. A hierarchical logit regression analysis was conducted to investigate the relationship between leisure walking and the prevalence of AD and dementia. The results show that leisure walking has been negatively associated with the prevalence of AD and other dementias-that is, they indicate that older adults who frequently engaged in leisure walking were less likely to develop AD and other dementias. This finding suggests the importance of leisure walking as a dementia prevention program for older adults.


Subject(s)
Alzheimer Disease , Aged , Alzheimer Disease/complications , Alzheimer Disease/epidemiology , Humans , Leisure Activities , Prevalence , Walking
4.
Transl Psychiatry ; 12(1): 283, 2022 07 14.
Article in English | MEDLINE | ID: covidwho-1931377

ABSTRACT

Emerging evidence has suggested a close correlation between COVID-19 and neurodegenerative disorders. However, whether there exists a causal association and the effect direction remains unknown. To examine the causative role of COVID-19 in the risk of neurodegenerative disorders, we estimated their genetic correlation, and then conducted a two-sample Mendelian randomization analysis using summary statistics from genome-wide association studies of susceptibility, hospitalization, and severity of COVID-19, as well as six major neurodegenerative disorders including Alzheimer's disease (AD), amyotrophic lateral sclerosis, frontotemporal dementia, Lewy body dementia, multiple sclerosis, and Parkinson's disease. We identified a significant and positive genetic correlation between hospitalization of COVID-19 and AD (genetic correlation: 0.23, P = 8.36E-07). Meanwhile, hospitalization of COVID-19 was significantly associated with a higher risk of AD (OR: 1.02, 95% CI: 1.01-1.03, P: 1.19E-03). Consistently, susceptibility (OR: 1.05, 95% CI: 1.01-1.09, P: 9.30E-03) and severity (OR: 1.01, 95% CI: 1.00-1.02, P: 0.012) of COVID-19 were nominally associated with higher risk of AD. The results were robust under all sensitivity analyses. These results demonstrated that COVID-19 could increase the risk of AD. Future development of preventive or therapeutic interventions could attach importance to this to alleviate the complications of COVID-19.


Subject(s)
Alzheimer Disease , COVID-19 , Neurodegenerative Diseases , Alzheimer Disease/epidemiology , Alzheimer Disease/genetics , Genome-Wide Association Study/methods , Humans , Mendelian Randomization Analysis/methods , Neurodegenerative Diseases/epidemiology , Neurodegenerative Diseases/genetics
5.
Biochim Biophys Acta Mol Basis Dis ; 1868(9): 166430, 2022 09 01.
Article in English | MEDLINE | ID: covidwho-1930739

ABSTRACT

Type I interferon (IFN-I) signalling represents a major target for modulation in a virus' bid for latency. IFN-I perturbations are also present in such as Alzheimer's disease (AD) and multiple sclerosis (MS), where viral infections are known to increase symptomatic burden. IFN-I modulation such as via IFNß-1a, an established MS treatment, has been researched to a limited extent to both AD and COVID-19. In this mini review, we present emerging research on trained immunity as a pathogenetic basis for Alzheimer's disease and the emerging context for IFNß-1a repositioning, via mechanisms shared with multiple sclerosis and induced by viral infections.


Subject(s)
Alzheimer Disease , COVID-19 , Multiple Sclerosis , Virus Diseases , Humans , Interferon-beta
6.
J Clin Lab Anal ; 36(7): e24483, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1929823

ABSTRACT

OBJECTIVE: This case-control study was designed to compare the composition of the predominant oral bacterial microbiome in Alzheimer's disease (AD) and control group. SUBJECT: A total of 30 adult participants (15 AD and 15 healthy individuals) were entered in this study. The composition of oral bacterial microbiome was examined by quantitative real-time polymerase chain reaction (qPCR) using bacterial 16S rDNA gene. The levels of systemic inflammatory cytokines in both groups were assessed using enzyme-linked immunosorbent assays (ELISA). RESULTS: The loads of Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia were significantly more abundant in the AD compared to the control group (p < 0.05). Although Aggregatibacter actinomycetemcomitans and Streptococcus mutans were relatively frequent in the AD group, no significance difference was observed in their copy number between two groups. Although the concentrations of IL-1, IL-6, and TNF-α were higher in the AD group, there was a significant difference in their levels between the two groups (p < 0.05). Finally, there was a significant relationship between increased number of pathogenic bacteria in oral microbiome and higher concentration of cytokines in patient's blood. CONCLUSION: Our knowledge of oral microbiome and its exact association with AD is rather limited; our study showed a significant association between changes in oral microbiome bacteria, increased inflammatory cytokines, and AD.


Subject(s)
Alzheimer Disease , Microbiota , Mouth , Adult , Aggregatibacter actinomycetemcomitans , Alzheimer Disease/microbiology , Case-Control Studies , Cytokines , Humans , Mouth/microbiology , Pilot Projects
8.
Eur Rev Med Pharmacol Sci ; 26(12): 4535-4544, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1924924

ABSTRACT

OBJECTIVE: The pandemic of Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues, and SARS-CoV-2 variants continue to emerge. In addition to typical fever and respiratory symptoms, many patients with COVID-19 experience a variety of neurological complications. In this review, we analyzed and reviewed the current status and possible mechanisms between COVID-19 and several typical neurodegenerative diseases, particularly Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, hoping to propose the potential direction of further research and concern. MATERIALS AND METHODS: Electronic literature search of the databases (Medline/PubMed, Web of Science, and Google Scholar). The keywords used were COVID-19, SARS-CoV-2, neurodegenerative disease, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The retrieved relevant articles were reviewed and critically analyzed. RESULTS: SARS-CoV-2 is a highly neuroinvasive neurotropic virus that invades cells through angiotensin-converting enzyme 2 (ACE2) receptor-driven pathway. SARS-CoV-2 neuroinvasion, neuroinflammation, and blood-brain barrier (BBB) dysfunction may contribute to the pathogenesis of neurodegenerative diseases. CONCLUSIONS: Some patients with neurodegenerative diseases have already shown more susceptibility to SARS-CoV-2 infection and significantly higher mortality due to the elderly population with underlying diseases. Moreover, SARS-CoV-2 could cause damage to the central nervous system (CNS) that may substantially increase the incidence of neurodegenerative diseases and accelerate the progression of them.


Subject(s)
Alzheimer Disease , Amyotrophic Lateral Sclerosis , COVID-19 , Neurodegenerative Diseases , Parkinson Disease , Aged , Humans , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2
9.
J Mol Graph Model ; 115: 108230, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1914638

ABSTRACT

Acetylcholinesterase (AChE) is one of the most important drug targets for Alzheimer's disease treatment. In this work, a combined approach involving machine-learning (ML) model and atomistic simulations was established to predict the ligand-binding affinity to AChE of the natural compounds from VIETHERB database. The trained ML model was first utilized to rapidly and accurately screen the natural compound database for potential AChE inhibitors. Atomistic simulations including molecular docking and steered-molecular dynamics simulations were then used to confirm the ML outcome. Good agreement between ML and atomistic simulations was observed. Twenty compounds were suggested to be able to inhibit AChE. Especially, four of them including geranylgeranyl diphosphate, 2-phosphoglyceric acid, and 2-carboxy-d-arabinitol 1-phosphate, and farnesyl diphosphate are highly potent inhibitors with sub-nanomolar affinities.


Subject(s)
Alzheimer Disease , Cholinesterase Inhibitors , Acetylcholinesterase/chemistry , Alzheimer Disease/drug therapy , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Humans , Machine Learning , Molecular Docking Simulation , Molecular Dynamics Simulation
10.
Front Immunol ; 13: 878201, 2022.
Article in English | MEDLINE | ID: covidwho-1892654

ABSTRACT

Coronavirus 2 (SARS-CoV2) (COVID-19) causes severe acute respiratory syndrome. Severe illness of COVID-19 largely occurs in older people and recent evidence indicates that demented patients have higher risk for COVID-19. Additionally, COVID-19 further enhances the vulnerability of older adults with cognitive damage. A balance between the immune and inflammatory response is necessary to control the infection. Thus, antimicrobial and anti-inflammatory drugs are hopeful therapeutic agents for the treatment of COVID-19. Accumulating evidence suggests that lactoferrin (Lf) is active against SARS-CoV-2, likely due to its potent antiviral and anti-inflammatory actions that ultimately improves immune system responses. Remarkably, salivary Lf levels are significantly reduced in different Alzheimer's disease (AD) stages, which may reflect AD-related immunological disturbances, leading to reduced defense mechanisms against viral pathogens and an increase of the COVID-19 susceptibility. Overall, there is an urgent necessity to protect AD patients against COVID-19, decreasing the risk of viral infections. In this context, we propose bovine Lf (bLf) as a promising preventive therapeutic tool to minimize COVID-19 risk in patients with dementia or AD.


Subject(s)
Alzheimer Disease , COVID-19 , Aged , Alzheimer Disease/complications , Animals , Anti-Inflammatory Agents , COVID-19/complications , COVID-19/drug therapy , Cattle , Humans , Lactoferrin/therapeutic use , SARS-CoV-2
11.
Alzheimer Dis Assoc Disord ; 35(2): 172-177, 2021.
Article in English | MEDLINE | ID: covidwho-1891231

ABSTRACT

In March 2020, the novel coronavirus (COVID-19) became a global pandemic that would cause most in-person visits for clinical studies to be put on pause. Coupled with protective stay at home guidelines, clinical research at the Icahn School of Medicine at Mount Sinai Alzheimer's Disease Research Center (ISMMS ADRC) needed to quickly adapt to remain operational and maintain our cohort of research participants. Data collected by the ISMMS ADRC as well as from other National Institute on Aging (NIA) Alzheimer Disease centers, follows the guidance of the National Alzheimer Coordinating Center (NACC). However, at the start of this pandemic, NACC had no alternative data collection mechanisms that could accommodate these safety guidelines. To stay in touch with our cohort and to ensure continued data collection under different stages of quarantine, the ISMMS ADRC redeployed their work force to continue their observational study via telehealth assessment. On the basis of this experience and that of other centers, NACC was able to create a data collection process to accommodate remote assessment in mid-August. Here we review our experience in filling the gap during this period of isolation and describe the adaptations for clinical research, which informed the national dialog for conducting dementia research in the age of COVID-19 and beyond.


Subject(s)
Alzheimer Disease/epidemiology , COVID-19/diagnosis , Data Collection , SARS-CoV-2/pathogenicity , Alzheimer Disease/complications , COVID-19/complications , COVID-19/virology , Dementia/complications , Humans
12.
Int J Mol Sci ; 23(11)2022 May 24.
Article in English | MEDLINE | ID: covidwho-1884204

ABSTRACT

Alzheimer's disease (AD) is a complex chronic disease of the brain characterized by several neurodegenerative mechanisms and is responsible for most dementia cases in the elderly. Declining immunity during ageing is often associated with peripheral chronic inflammation, and chronic neuroinflammation is a constant component of AD brain pathology. In the Special Issue published in 2021 eight papers were collected regarding different aspects of neurodegeneration associated with AD. Five papers presented and discussed infectious agents involved in brain AD pathology and three discussed data regarding receptors regulation and possible treatment of the disease. Below I will discuss and further elaborate on topics related to infections, inflammation, and neurodegenerative pathways in AD and brain senescence. The topic presented here may contribute to early intervention protocols for preventing or slowing the progression of cognitive deterioration in the elderly.


Subject(s)
Alzheimer Disease , Cognition Disorders , Aged , Alzheimer Disease/metabolism , Brain/metabolism , Humans , Inflammation/complications , Neurons/metabolism
14.
Comput Biol Med ; 146: 105657, 2022 07.
Article in English | MEDLINE | ID: covidwho-1850907

ABSTRACT

Alzheimer's disease (AD) is the leading cause of dementia globally, with a growing morbidity burden that may exceed diagnosis and management capabilities. The situation worsens when AD patient fatalities are exposed to COVID-19. Because of differences in clinical features and patient condition, a patient's recovery from COVID-19 with or without AD varies greatly. Thus, this situation stimulates a spectrum of imbalanced data. The inclusion of different features in the class imbalance offers substantial problems for developing of a classification framework. This study proposes a framework to handle class imbalance and select the most suitable and representative datasets for the hybrid model. Under this framework, various state-of-the-art resample techniques were utilized to balance the datasets, and three sets of data were finally selected. We developed a novel hybrid deep learning model AD-CovNet using Long Short-Term Memory (LSTM) and Multi-layer Perceptron (MLP) algorithms that delineate three unique datasets of COVID-19 and AD-COVID-19 patient fatality predictions. This proposed model achieved 97% accuracy, 97% precision, 97% recall, and 97% F1-score for Dataset I; 97% accuracy, 97% precision, 96% recall, and 96% F1-score for Dataset II; and 86% accuracy, 88% precision, 88% recall, and 86% F1-score for Dataset III. In addition, AdaBoost, XGBoost, and Random Forest models were utilized to evaluate the risk factors associated with AD-COVID-19 patients, and the outcome outperformed diagnostic performance. The risk factors predicted by the models showed significant clinical importance and relevance to mortality. Furthermore, the proposed hybrid model's performance was evaluated using a statistical significance test and compared to previously published works. Overall, the uniqueness of the large dataset, the effectiveness of the deep learning architecture, and the accuracy and performance of the hybrid model showcase the first cohesive work that can formulate better predictions and help in clinical decision-making.


Subject(s)
Alzheimer Disease , COVID-19 , Deep Learning , Humans , Neural Networks, Computer , Risk Factors
15.
Dementia (London) ; 21(5): 1734-1752, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1846732

ABSTRACT

The COVID-19 pandemic has placed a tremendous burden on all of society, particularly among vulnerable populations such as people living with dementia and their caregivers. Efforts to understand the impact of the COVID-19 pandemic on those living with dementia are crucial towards addressing needs during the pandemic and beyond. This qualitative descriptive study includes a thematic analysis of 6938 tweets from March 17-24, 2020, that included direct or indirect references to COVID-19 and at least one of the following terms/hashtags: Alzheimer, #Alzheimer, dementia, and #dementia. Five themes were identified: continuing care, finding support, preventing spread of COVID-19, maintaining human rights, and the impact of the pandemic on the daily lives of people living with dementia. People living with dementia and their families faced unique challenges related to caregiving, maintaining social connectedness while trying to follow public health guidelines, and navigating the convergence of COVID-19 and dementia-related stigma. Data from Twitter can be an effective means to understand the impacts of public health emergencies among those living with dementia and how to address their needs moving forward by highlighting gaps in practice, services, and research.


Subject(s)
Alzheimer Disease , COVID-19 , Dementia , Social Media , COVID-19/epidemiology , Humans , Pandemics
16.
J Prev Alzheimers Dis ; 9(2): 277-285, 2022.
Article in English | MEDLINE | ID: covidwho-1841706

ABSTRACT

BACKGROUND: Widespread lifestyle risk reduction at the community level is considered effective in decreasing Alzheimer's disease (AD). To address the limited use of risk deduction in AD, this study aimed to explore the feasibility of community-level implementation. Diverse older adults (60+) living in Richmond, VA, with incomes below $12,000/year and managing diabetic/cardiovascular symptoms were offered weekly lifestyle telephone-health coaching for 12-weeks in 2019-2020 (Phase 1). The health coaching sessions were framed to provide AD lifestyle risk reduction education, goal setting, and support: motivations and self-efficacy. The study sample (n=40, mean age 68 years (range: 60-76 years)) was 90% African American/Black (n=36), 100% Non-Hispanic, and 45% males (n=18). Twenty-five participants (60%) reported experiencing some/often memory problems in the last 12-months. Thirty-nine (95%) of subjects successfully participated in coaching sessions; on average, 11 (91.9%) sessions per subject were completed. Participants provided positive anecdotal feedback and stated the need for continued health coaching. Consequently, n=30 (75%) of the original sample consented to continued health coaching during the 2020-2021 COVID-19 pandemic (Phase 2). All study subjects were examined at baseline (Time 1), 3-month (Time 2), covid-baseline (Time 3), and 3-months postcovid-baseline (Time 4). Repeated Measures ANOVAs were done to examine Time and Time*Memory Status effects. RESULTS: There was a total risk reduction at Phase 1 (F=9.26; p=.004; effect size=.19). At Phase 2, alcohol use decreased (p=.05), quadratic time effects were observed in physical activity (p=.01-.02), and cubic time effects were observed in depression (p=.02). Overall, total risk reduction in Phase 2 was observed at F=5.05; p=.03 effect size=.16. Pre/post-test analyses indicated improvement in Memory Problem Time Interaction (p=.007), AD knowledge (p=.01-.03), and Tired Days (p=.04) across Phase 1. There was also improvement in Social Isolation Time Interaction (p=.03); Tobacco Addiction (p=.001); Poor Mental Health Days (p=.05), and Worried Days Time Interaction (p=.02-.01) across Phase 2. Between subject Memory Status effects, indicating poorer baseline levels for individuals reporting memory problems had greater improvement seen in memory complaints (p=.001), poor mental health days (.02), and tired days (.003-.01). CONCLUSIONS: This preliminary work creates the impetus for future large-scale lifestyle AD risk reduction investigations to mitigate and improve modifiable AD risk among low-income, diverse older adults, including individuals reporting memory problems. Our findings surrounding participant engagement and positive trends in AD risk reduction support the hypothesis that telephone-based health coaching is a practical and feasible AD risk reduction intervention.


Subject(s)
Alzheimer Disease , COVID-19 , Mentoring , Aged , Alzheimer Disease/prevention & control , Female , Humans , Male , Pandemics , Telephone
18.
Neuroimage Clin ; 34: 103002, 2022.
Article in English | MEDLINE | ID: covidwho-1821425

ABSTRACT

PURPOSE: Cerebral amyloid angiopathy (CAA) is a common neuropathological finding and clinical entity that occurs independently and with co-existent Alzheimer's disease (AD) and small vessel disease. We compared diffusion tensor imaging (DTI) metrics of the fornix, the primary efferent tract of the hippocampus between CAA, AD and Mild Cognitive Impairment (MCI) and healthy controls. METHODS: Sixty-eight healthy controls, 32 CAA, 21 AD, and 26 MCI patients were recruited at two centers. Diffusion tensor images were acquired at 3 T with high spatial resolution and fluid-attenuated inversion recovery (FLAIR) to suppress cerebrospinal fluid (CSF) and minimize partial volume effects on the fornix. The fornix was delineated with deterministic tractography to yield mean diffusivity (MD), axial diffusivity (AXD), radial diffusivity (RD), fractional anisotropy (FA) and tract volume. Volumetric measurements of the hippocampus, thalamus, and lateral ventricles were obtained using T1-weighted MRI. RESULTS: Diffusivity (MD, AXD, and RD) of the fornix was highest in AD followed by CAA compared to controls; the MCI group was not significantly different from controls. FA was similar between groups. Fornix tract volume was âˆ¼ 30% lower for all three patient groups compared to controls, but not significantly different between the patient groups. Thalamic and hippocampal volumes were preserved in CAA, but lower in AD and MCI compared to controls. Lateral ventricular volumes were increased in CAA, AD and MCI. Global cognition, memory, and executive function all correlated negatively with fornix diffusivity across the combined clinical group. CONCLUSION: There were significant diffusion changes of the fornix in CAA, AD and MCI compared to controls, despite relatively intact thalamic and hippocampal volumes in CAA, suggesting the mechanisms for fornix diffusion abnormalities may differ in CAA compared to AD and MCI.


Subject(s)
Alzheimer Disease , Cerebral Amyloid Angiopathy , Cognitive Dysfunction , Alzheimer Disease/pathology , Anisotropy , Cognitive Dysfunction/complications , Cognitive Dysfunction/diagnostic imaging , Diffusion Tensor Imaging/methods , Fornix, Brain/diagnostic imaging , Fornix, Brain/pathology , Humans
19.
Mar Drugs ; 20(4)2022 Apr 02.
Article in English | MEDLINE | ID: covidwho-1810015

ABSTRACT

This paper examined the toxins naturally produced by marine dinoflagellates and their effects on increases in ß-amyloid plaques along with tau protein hyperphosphorylation, both major drivers of Alzheimer's disease (AD). This approach is in line with the demand for certain natural compounds, namely those produced by marine invertebrates that have the potential to be used in the treatment of AD. Current advances in AD treatment are discussed as well as the main factors that potentially affect the puzzling global AD pattern. This study focused on yessotoxins (YTXs), gymnodimine (GYM), spirolides (SPXs), and gambierol, all toxins that have been shown to reduce ß-amyloid plaques and tau hyperphosphorylation, thus preventing the neuronal or synaptic dysfunction that ultimately causes the cell death associated with AD (or other neurodegenerative diseases). Another group of toxins described, okadaic acid (OA) and its derivatives, inhibit protein phosphatase activity, which facilitates the presence of phosphorylated tau proteins. A few studies have used OA to trigger AD in zebrafish, providing an opportunity to test in vivo the effectiveness of new drugs in treating or attenuating AD. Constraints on the production of marine toxins for use in these tests have been considered. Different lines of research are anticipated regarding the action of the two groups of toxins.


Subject(s)
Alzheimer Disease , Dinoflagellida , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Amyloid beta-Peptides , Animals , Dinoflagellida/metabolism , Marine Toxins/pharmacology , Okadaic Acid/pharmacology , Plaque, Amyloid , Zebrafish/metabolism , tau Proteins/metabolism
20.
J Neural Transm (Vienna) ; 129(7): 847-859, 2022 07.
Article in English | MEDLINE | ID: covidwho-1797629

ABSTRACT

Individuals with Alzheimer's disease and other neurodegenerative diseases have been exposed to excess risk by the COVID-19 pandemic. COVID-19's main manifestations include high body temperature, dry cough, and exhaustion. Nevertheless, some affected individuals may have an atypical presentation at diagnosis but suffer neurological signs and symptoms as the first disease manifestation. These findings collectively show the neurotropic nature of SARS-CoV-2 virus and its ability to involve the central nervous system. In addition, Alzheimer's disease and COVID-19 has a number of common risk factors and comorbid conditions including age, sex, hypertension, diabetes, and the expression of APOE ε4. Until now, a plethora of studies have examined the COVID-19 disease but only a few studies has yet examined the relationship of COVID-19 and Alzheimer's disease as risk factors of each other. This review emphasizes the recently published evidence on the role of the genes of early- or late-onset Alzheimer's disease in the susceptibility of individuals currently suffering or recovered from COVID-19 to Alzheimer's disease or in the susceptibility of individuals at risk of or with Alzheimer's disease to COVID-19 or increased COVID-19 severity and mortality. Furthermore, the present review also draws attention to other uninvestigated early- and late-onset Alzheimer's disease genes to elucidate the relationship between this multifactorial disease and COVID-19.


Subject(s)
Alzheimer Disease , COVID-19 , Alzheimer Disease/epidemiology , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Humans , Pandemics , Risk Factors , SARS-CoV-2
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