Prevention Of Alzheimer's Disease Research Articles

Estradiol enhanced neuronal plasticity and ameliorated astrogliosis in human iPSC-derived neural models

Introduction17β-Estradiol (E2) is a sex hormone that has been previously demonstrated to have neurotherapeutic effects on animal models of Alzheimer's disease (AD). However, clinical trials on E2 replacement therapy for preventing AD onset yielded inconsistent results. Therefore, it is imperative to clarify the therapeutic effects of E2 on human cells. In this study, we utilized induced pluripotent stem cells (iPSCs) derived from multiple AD donors to explore the therapeutic effects of E2 on the in vitro model of human cells. MethodsWe conducted a systematic review and meta-analysis using a random-effects model of the previously reported AD clinical trials to summarize the effects of E2 replacement therapy on AD prevention. Subsequently, we induced iPSCs from the donors of the healthy control (1210B2 line (female) and 201B7 line (female)), the familial AD (APP V717L line (female) and APP KM670/671NL line (female)), and the sporadic AD (UCSD-SAD3.7 line (APOE ε3/ε3) (male), UCSD-SAD7D line (APOE ε3/ε4) (male), and TMGH-1 line (APOE ε3/ε3) (female)), then differentiated to neurons. In addition to the mono-culture model of the neurons, we also examined the effects of E2 on the co-culture model of neurons and astrocytes. ResultsThe meta-analysis of the clinical trials concluded that E2 replacement therapy reduced the risk of AD onset (OR, 0.69; 95 % confidence interval [CI], 0.53–0.91; I2 = 82 %). Neural models from the iPSCs of AD donors showed an increase in secreted amyloid-beta (Aβ) levels in the mono-culture model and an astrogliosis-like phenotype in the co-culture model. E2 treatment to the neuronal models derived from the iPSCs enhanced neuronal activity and increased neurite complexity. Furthermore, E2 treatment of the co-culture model ameliorated the astrogliosis-like phenotype. However, in contrast to the previous reports using mouse models, E2 treatment did not change AD pathogenesis, including Aβ secretion and phosphorylated tau (pTau) accumulation. ConclusionE2 treatment of the human cellular model did not impact Aβ secretion and pTau accumulation, but promoted neuronal plasticity and alleviated the astrogliosis-like phenotype. The limited effects of E2 may give a clue for the mixed results of E2 clinical trials.

Modulation of Tau Pathology in Alzheimer's Disease by Dietary Bioactive Compounds.

Tau is a microtubule-associated protein essential for microtubule assembly and stability in neurons. The abnormal intracellular accumulation of tau aggregates is a major characteristic of brains from patients with Alzheimer's disease (AD) and other tauopathies. In AD, the presence of neurofibrillary tangles (NFTs), which is composed of hyperphosphorylated tau protein, is positively correlated with the severity of the cognitive decline. Evidence suggests that the accumulation and aggregation of tau cause synaptic dysfunction and neuronal degeneration. Thus, the prevention of abnormal tau phosphorylation and elimination of tau aggregates have been proposed as therapeutic strategies for AD. However, currently tau-targeting therapies for AD and other tauopathies are limited. A number of dietary bioactive compounds have been found to modulate the posttranslational modifications of tau, including phosphorylation, small ubiquitin-like modifier (SUMO) mediated modification (SUMOylation) and acetylation, as well as inhibit tau aggregation and/or promote tau degradation. The advantages of using these dietary components over synthetic substances in AD prevention and intervention are their safety and accessibility. This review summarizes the mechanisms leading to tau pathology in AD and highlights the effects of bioactive compounds on the hyperphosphorylation, aggregation and clearance of tau protein. The potential of using these bioactive compounds for AD prevention and intervention is also discussed.

Drug repurposing for neurodegenerative diseases using Zebrafish behavioral profiles

Drug repurposing can accelerate drug development while reducing the cost and risk of toxicity typically associated with de novo drug design. Several disorders lacking pharmacological solutions and exhibiting poor results in clinical trials - such as Alzheimer’s disease (AD) - could benefit from a cost-effective approach to finding new therapeutics. We previously developed a neural network model, Z-LaP Tracker, capable of quantifying behaviors in zebrafish larvae relevant to cognitive function, including activity, reactivity, swimming patterns, and optomotor response in the presence of visual and acoustic stimuli. Using this model, we performed a high-throughput screening of FDA-approved drugs to identify compounds that affect zebrafish larval behavior in a manner consistent with the distinct behavior induced by calcineurin inhibitors. Cyclosporine (CsA) and other calcineurin inhibitors have garnered interest for their potential role in the prevention of AD. We generated behavioral profiles suitable for cluster analysis, through which we identified 64 candidate therapeutics for neurodegenerative disorders.

Apple Pomace Extract Improves MK-801-Induced Memory Impairment in Mice.

Alzheimer's disease (AD) is a neurodegenerative disease that involves progressive cognitive decline accompanied by synaptic degeneration and impaired neurotransmission. Recent studies revealed that apple pomace, a waste byproduct of the apple processing industry, has beneficial health properties, but its potential to prevent and treat AD has not been determined. Herein, we examined the effects of apple pomace extract on N-methyl-D-aspartate receptor antagonist MK-801-induced memory impairment in mice. Repeated treatment with apple pomace extract for 7 days reversed the MK-801-induced impairment of associative memory and recognition memory. RNA sequencing revealed that repeated treatment with apple pomace extract altered the gene expression profile in the hippocampus of mice. Real-time PCR showed that apple pomace extract induced upregulation of the mRNA expression for Zfp125 and Gstp1. Furthermore, gene sets related to synapse and neurotransmission were upregulated by apple pomace extract. These findings indicate that apple pomace extract may be useful for the prevention and treatment of AD.

Therapeutic Effects of the major alkaloid constituents of Evodia rutaecarpa in Alzheimer's disease.

Since the report of Alzheimer's disease (AD) in 1907, it has garnered widespread attention due to its intricate pathogenic mechanisms, significant impact on patients' lives, and the substantial burden it places on society. Presently, effective treatments for AD remain elusive. Recent pharmacological studies on the traditional East Asian herb, Evodia rutaecarpa, have revealed that the bioactive alkaloid components within it can ameliorate AD-related cognitive impairments and neurological damage through various pathways, including anti-inflammatory, antioxidant, and anti-acetylcholinesterase activities. Consequently, this article provides an overview of the pharmacological effects and research status of the four main alkaloid components found in Evodia concerning AD. We hope this article will serve as a valuable reference for experimental and clinical research on the use of Evodia in AD prevention and treatment.

Evaluation of the beneficial effects of ETAS® on normal aging or mild cognitive impairment subjects: A pilot randomized controlled trial

Context: Recently, new intervention tools at the mild cognitive impairment (MCI) stage are needed to prevent dementia, including Alzheimer's disease (AD). Aims: To evaluate whether a standardized Asparagus officinalis stem (ETAS) extract, as a functional ingredient, effectively maintains cognitive functions in subjects with normal aging and MCI. Methods: A pilot randomized controlled trial was conducted on thirty subjects that were randomly allocated to the experimental group (n = 15), which received ETAS supplementation (1,000 mg) daily, and a control group, which received placebo (dextrin) in the same form (n = 15) for a period of 12 months. All subjects were evaluated using neuropsychological questionnaires comprised of Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), Clock Drawing Test (CDT), and Hospital Anxiety and Depression Scale (HADS) at all visit times. Brain tests (MRI, EEG and EPB) and blood tests (hematology, hemochemistry, immunological status and HSP70) were also performed. Primary endpoints were the change in the neuropsychological questionnaire scores. Secondary endpoints such as immunological and molecular biomarkers of dementia, neurological imaging, and electrophysiological outcomes were measured. Results: The ETAS group showed a significant improvement in scores on MMSE, FAB, and HADS, tended to improve in scores on CDT, and could show a slight increase in blood HSP70. The ETAS group also maintained normal levels of CD4/CD8 immune complex. No adverse events were detected during the study period. Conclusions: ETAS supplementation could prevent the progression of cognitive decline and anxiety/depression expression associated with the prevention of AD.

Global Burden of Alzheimer's Disease and Other Dementias Attributed to High Fasting Plasma Glucose from 1990 to 2019.

Burden of Alzheimer's disease (AD) and other dementias have grown rapidly over the decades, and high fasting plasma glucose (HFPG) was one of the well-established risk factors. It is urgently needed to estimate the global burden of AD and other dementias attributable to high fasting plasma glucose between regions, countries, age groups, and sexes to inform development of effective primary disease prevention strategies and intervention policies. The burden of AD and other dementias attributable to HFPG was estimated based on a modeling strategy using the Global Burden of Disease Study 2019 dataset. The disease burden and time trend globally and by region, country, development level, age group, and sex were evaluated. The number of AD and other dementias-related deaths attributable to HFPG increased from 42,998.23 (95% uncertainty interval, UI: 4459.86-163,455.78, the year of 1990) to 159,244.53 deaths (95% UI 18,385.23-583,514.15, the year of 2019). The age-standardized death rate increased from 1.69 (95% UI 0.18-6.54) in 1990 to 2.24 (95% UI 0.26-8.24) in 2019. The burden was higher in more developed regions. The burden in women was double that in men, that HFPG-attributable AD and other dementias caused 99,812.79 deaths (95% UI 9005.67-387,160.60) in women and 59,431.74 deaths (95% UI 5439.02-214,819.23) in men, with age-standardized death rate of 2.27 (95% UI 0.20-8.79) per 100,000 population in women and 2.20 (95% UI 0.20-8.00) in men. Findings from the current study emphasizes the urgent requirement for targeted interventions in high-development regions, as well as the importance of proactive measures in middle-development countries in protection of AD and other dementias. The gender disparity necessitates the integration of gender-specific considerations in targeted approaches in prevention of AD and other dementias.

Plant Soup Formulations Show Cholinesterase Inhibition Potential in the Prevention of Alzheimer's Disease.

As the cholinesterase theory is a prominent hypothesis underlying our current understanding of Alzheimer's disease (AD), the goal of this study was to compose functional vegan lunchtime soups with potential health benefits in the prevention of AD (in the context of cholinesterase inhibition). The potential of 36 edible plant raw materials in terms of acetyl- and butyrylcholinesterase inhibition was investigated using a 96-well microplate reader. The most promising ingredients were combined to obtain 18 palatable vegetable soup recipes with 6 dominant flavor, appearance, and aroma variants. To shortlist candidates for in-depth analysis and potential consideration in industrial production, our team performed a sensory analysis of the soups. The white boletus soup exhibited the highest potential for cholinesterase inhibition, further bolstered by the inclusion of other ingredients known for their elevated capacity to inhibit both AChE and BChE. Ingredients such as blackthorn (Prunus spinosa), garlic, and white potato contributed significantly to this inhibitory effect (nearly 100% of AChE inhibition). Notably, intriguing results were also observed for asparagus soup, despite the fact that the inhibitory potential of asparagus itself is negligible compared to other raw materials. The success of the asparagus soup lies in the meticulous selection of various ingredients, each contributing to its overall effectiveness. It was observed that mushroom soups scored the highest in this respect, while the team members' response to nettle soup was the least favorable. The outcomes of our study should serve as a catalyst for further exploration of this important research domain. Our current research focuses on deeper insights into the potential of comprehensive meal options. Furthermore, the synergy/antagonism/non-interaction between respective soup ingredients as well as elements of individual soups' chemical composition is a very interesting topic currently under our intensive scientific investigation.

Usability of a Web-Based Registry for Preclinical Alzheimer's Disease: Implications from a Cross-Sectional Online Survey.

We have been conducting a Japanese trial-ready cohort web study since 2019 as a web-based online registry to enroll individuals with preclinical Alzheimer's disease to facilitate trials on Alzheimer's disease prevention. The usability of a website might be an important factor in determining user participation and retention. We conducted a user questionnaire survey to analyze the usability of the Japanese trial-ready cohort website and user characteristics for future website improvement. This was a cross-sectional prospective observational study. Online survey using Google Forms. Among the Japanese trial-ready cohort web study participants, we enrolled those who provided consent to participate in the study and had completed one or more Cognitive Function Instrument tests before May 2, 2023. We sent an invitation e-mail, including the questionnaire web address, to eligible participants on July 21 and 22, 2023. We analyzed the questionnaire answers, including the system usability scale score and time of response (in 24 h). We also compared the respondents' characteristics with that of all the Japanese trial-ready cohort web study participants to identify features associated with an increased/decreased response rate to the questionnaire. Among the 10,112 Japanese trial-ready cohort web study participants that we sent invitation e-mails, we received 1,574 eligible responses (15.6%) within three weeks of the response acceptance period. The mean system usability scale score was 67.6, and no difference in system usability scale scores was observed in terms of age or sex. Approximately half of the respondents of the Japanese trial-ready cohort web study heard about it online, whereas one-fourth heard about it via newspapers. Contribution to drug development for dementia treatment was the most frequent motivation for participating in the Japanese trial-ready cohort web study (51.5%), followed by participation in the latest research (48.1%), concerns about self-memory (43.4%), and a family history of dementia (34.6%). Female respondents responded approximately 1.5 h later than male respondents. Lastly, those who had participated in the Japanese trial-ready cohort onsite study, were in their 70's, or had a larger number of Cognitive Function Instrument or Cogstate tests completion history were more likely to respond to the current online survey (relative risk of response > 1). We conducted an online survey using Google Forms for participants in the Japanese trial-ready cohort web study to determine the usability. The results of this study might help to improve the user experience of the Japanese trial-ready cohort website itself, increase the web study registrants, maintain user retention, facilitate future online surveys, and serve as a reference for other web-based registries of presymptomatic disease status.

The Mediterranean-dietary approaches to stop hypertension diet intervention for neurodegenerative delay (MIND) diet: a bibliometric analysis.

The MIND diet is a healthy dietary pattern that has some benefits for many health outcomes. Our study aims to conduct a bibliometric analysis of the MIND diet, identifying leading edges and hotspots to provide a reference for future research. The research on the MIND diet was gathered from the Web of Science Core Collection (WOSCC) database. For bibliometric analysis, VOSviewer 1.6.16 and the WOSCC Online Analysis Platform were utilized. In total, this comprehensive investigation encompassed 171 documents in the field of the MIND diet. The publications are globally distributed, with contributions from 953 authors across 362 institutions in 37 countries/regions, and published in 94 journals. The United States leads with 72 publications, and Iran and the People's Republic of China also show notable engagement with 28 and 19 publications, respectively. Rush University stands out with 21 publications, followed by Harvard University and Tehran University of Medical Sciences, demonstrating their substantial contributions to this field. Martha Clare Morris is a key figure with 10 publications, alongside Klodian Dhana and Puja Agarwal, each contributing 9 publications, highlighting their influence in the MIND diet research. The journal "Nutrients" is a major publication venue with 20 related articles, followed by "Frontiers in Nutrition" and "Journal of Nutrition Health Aging," reflecting their crucial roles in advancing knowledge about the MIND diet. The first high-cited publication was published in Alzheimers & Dementia and conducted by Martha Clare Morris, which focuses on the MIND diet's relationship with Alzheimer's disease prevention and cognitive decline and emphasizes the diet's neuroprotective potential, highlighting how even moderate adherence can substantially reduce Alzheimer's risk and slow cognitive decline. In conclusion, this is the first comprehensive bibliometric study that quantitatively and qualitatively analyzed the publications in the field of the MIND diet. The MIND diet may be a promising dietary pattern for dementia. However, the current evidence is restricted and highlights the urgency and necessity of further research to investigate the efficacy of this diet for cognitive function. In addition, the MIND diet may have some benefits for other health outcomes, including CVDs, cancer, and diabetes. The number of studies in the field of the MIND diet is limited. More studies are needed, and will give us more knowledge about the MIND diet to improve human health, especially for dementia.

Alzheimer's Disease Prevention and Treatment Based on Population-Based Approaches.

The development of effective prevention and treatment strategies for Alzheimer's disease (AD) and dementia is hindered by limited knowledge of the underlying biological and environmental causes. While certain genetic factors have been associated with AD, and various lifestyle and environmental factors have been linked to dementia risk, the interactions between genes and the environment are not yet fully understood. To identify new avenues for dementia prevention, coordinated global efforts are needed to utilize existing cohorts and resources effectively and efficiently. This chapter provides an overview of current research on risk and protective factors for AD and dementia and discusses the opportunities and challenges associated with population-based approaches.

Exosome and prevention of Alzheimer's disease: based on theory of kidney storing essence

The theory of kidney storing essence storage, an important part of the basic theory of traditional Chinese medicine(TCM), comes from the Chapter 9 Discussion on Six-Plus-Six System and the Manifestations of the Viscera in the Plain Questions, which says that "the kidney manages closure and is the root of storage and the house of Jing(Essence)". According to this theory, essence is the fundamental substance of human life activities and it is closely related to the growth and development of the human body. Alzheimer's disease(AD) is one of the common neurodegenerative diseases, with the main pathological features of Aβ deposition and Tau phosphorylation, which activate neurotoxic reactions and eventually lead to neuronal dysfunction and cell death, severely impairing the patient's cognitive and memory functions. Although research results have been achieved in the TCM treatment of AD, the complex pathogenesis of AD makes it difficult to develop the drugs capable of curing AD. The stem cell therapy is an important method to promote self-repair and regeneration, and bone marrow mesenchymal stem cells(BMSCs) as adult stem cells have the ability of multi-directional differentiation. By reviewing the relevant literature, this paper discusses the association between BMSCs and the TCM theory of kidney storing essence, and expounds the material basis of this theory from the perspective of molecular biology. Studies have shown that TCM with the effect of tonifying the kidney in the treatment of AD are associated with BMSCs. Exosomes produced by such cells are one of the main substances affecting AD. Exosomes containing nucleic acids, proteins, and lipids can participate in intercellular communication, regulate cell function, and affect AD by reducing Aβ deposition, inhibiting Tau protein phosphorylation and neuroinflammation, and promoting neuronal regeneration. Therefore, discussing the prevention and treatment of exosomes and AD based on the theory of kidney storing essence will provide a new research idea for the TCM treatment of AD.

Deregulation of the Glymphatic System in Alzheimer's Disease: Genetic and Non-Genetic Factors.

Alzheimer's disease (AD) is the most prevalent form of dementia and is characterized by progressive degeneration of brain function. AD gradually affects the parts of the brain that control thoughts, language, behavior and mental function, severely impacting a person's ability to carry out daily activities and ultimately leading to death. The accumulation of extracellular amyloid-β peptide (Aβ) and the aggregation of intracellular hyperphosphorylated tau are the two key pathological hallmarks of AD. AD is a complex condition that involves both non-genetic risk factors (35%) and genetic risk factors (58-79%). The glymphatic system plays an essential role in clearing metabolic waste, transporting tissue fluid, and participating in the immune response. Both non-genetic and genetic risk factors affect the glymphatic system to varying degrees. The main purpose of this review is to summarize the underlying mechanisms involved in the deregulation of the glymphatic system during the progression of AD, especially concerning the diverse contributions of non-genetic and genetic risk factors. In the future, new targets and interventions that modulate these interrelated mechanisms will be beneficial for the prevention and treatment of AD.

A ratiometric fluorescent probe revealing the abnormality of acetylated tau by visualizing polarity in Alzheimer's disease.

Abnormal neuronal polarity leads to early deficits in Alzheimer's disease (AD) by affecting the function of axons. Precise and rapid evaluation of polarity changes is very important for the early prevention and diagnosis of AD. However, due to the limitations of existing detection methods, the mechanism related to how neuronal polarity changes in AD is unclear. Herein, we reported a ratiometric fluorescent probe characterized by neutral molecule to disclose the polarity changes in nerve cells and the brain of APP/PS1 mice. Cy7-K showed a sensitive and selective ratiometric fluorescence response to polarity. Remarkably, unlike conventional intramolecular charge transfer fluorescent probes, the fluorescence quantum yield of Cy7-K in highly polar solvents is higher than that in low polar solvents due to the transition of neutral quinones to aromatic zwitterions. Using the ratiometric fluorescence imaging, we found that beta-amyloid protein (Aβ) inhibits the expression of histone deacetylase 6, thereby increasing the amount of acetylated Tau protein (AC-Tau) and ultimately enhancing cell polarity. There was a high correlation between polarity and AC-Tau. Furthermore, Cy7-K penetrated the blood-brain barrier to image the polarity of different brain regions and confirmed that APP/PS1 mice had higher polarity than Wild-type mice. The probe Cy7-K will be a promising tool for assessing the progression of AD development by monitoring polarity.

Potential role of nobiletin in Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid plaques and neurofibrillary tangles. At present, there is no specific drugs for the prevention and treatment of AD, so it is urgent to find natural products contributing to alleviation of AD. Nobiletin is one of polymethoxyflavones (PMFs) extracted mainly from citrus peels. Nobiletin has multiple bioactivities, good bioavailability and low side effects. Studies have shown that nobiletin improves cognitive impairment and pathological features in animal models of AD and exerts neuroprotective effects. In addition, 5-demethylnobiletin (5-DN), the main derivative of nobiletin, achieves neuroprotection through anti-inflammatory, neurotrophic and cholinergic effects for the treatment of neurodegenerative diseases. Other PMFs (for example tangeretin) also have the potential to prevent neurodegenerative diseases due to their anti-inflammatory and neuroprotective effects similar to nobiletin. Taken together, PMFs, including nobiletin, have potential as therapeutic agents for AD.

Potential role of herbal plants and beta sitosterol as a bioactive constituent in circumventing Alzheimer’s Disease

Alzheimer's Disease (AD), a neurological ailment, mostly affects the older population all around the world. The rational therapies show limited efficacy, adverse effects, and poor patient compliance; therefore, herbal drugs are considered a suitable supplement to the drug therapy for the treatment of AD. According to research, herbal drugs reduce symptoms of AD and also improve brain functioning through the inhibition of beta amyloid, gamma-secretase, and acetylcholine, along with the regulation of antioxidants and the activation of alpha-secretase. Various herbal plants like Salvia officinalis L., Bertholletia excelsa L., Withania somnifera L., and Urtica dioica L. help slow down the progression of AD by scavenging free radicals, inhibiting lipid peroxidation, beta amyloid and tau phosphorylation. Beta sitosterol, a phytosterol found abundantly in plants, has the ability to cross the Blood Brain Barrier and thus acts as a bioactive constituent in circumventing various neurological disorders. Numerous in vitro and in vivo investigations indicate that beta sitosterol shows immunomodulatory, lipid-lowering, as well as antioxidant properties. The plant sterol, beta sitosterol, has the capacity to decrease beta-amyloid platelet synthesis, indicating that it might be helpful in the treatment and prevention of AD. Treatment with beta-sitosterol can lessen plaque burden and also enhance spatial learning and recognition abilities in patients suffering from AD.

Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE ε4 homozygotes.

Alzheimer's Prevention Initiative Generation Study 1 evaluated amyloid beta (Aβ) active immunotherapy (vaccine) CAD106 and BACE-1 inhibitor umibecestat in cognitively unimpaired 60- to 75-year-old participants at genetic risk for Alzheimer's disease (AD). The study was reduced in size and terminated early. Results from the CAD106 cohort are presented. Sixty-five apolipoprotein E ε4 homozygotes with/without amyloid deposition received intramuscular CAD106 450μg (n=42) or placebo (n=23) at baseline; Weeks 1, 7, 13; and quarterly; 51 of them had follow-up Aβ positron emission tomography (PET) scans at 18 to 24 months. CAD106 induced measurable serum Aβ immunoglobulin G titers in 41/42 participants, slower rates of Aβ plaque accumulation (mean [standard deviation] annualized change from baseline in amyloid PET Centiloid: -0.91[5.65] for CAD106 versus 8.36 [6.68] for placebo; P<0.001), and three amyloid-related imaging abnormality cases (one symptomatic). Despite early termination, these findings support the potential value of conducting larger prevention trials of Aβ active immunotherapies in individuals at risk for AD. This was the first amyloid-lowering prevention trial in persons at genetic risk of late-onset Alzheimer's disease (AD). Active immunotherapy targeting amyloid (CAD106) was tested in this prevention trial. CAD106 significantly slowed down amyloid plaque deposition in apolipoprotein E homozygotes. CAD106 was generally safe and well tolerated, with only three amyloid-related imaging abnormality cases (one symptomatic). Such an approach deserves further evaluation in larger AD prevention trials.

Beneficial Fruit-Derived Phytochemicals in Treating Alzheimer’s Disease – A Review

Fruits, as a major source of nutrition have been investigated for their emerging evidence of several neuroprotective activities beneficial to Alzheimer’s disease (AD). This paper discusses recent evidence suggesting several fruit-derived bioactive substances that possess anti-AD activity. The original articles from 2011–2022 were collected from Pubmed and Scopus with related keywords and filtered. Several fruit constituents have shown significant inhibitory action against β-amyloid and tau hyperphosphorylation, either directly or indirectly via secretase inhibition. Some were also found to be cholinesterase inhibitors with specific antioxidative roles, disruptors of the neuroinflammation system, and promoters of neurogenesis and the neurogenic process. Many fruit phytochemicals remarkably alter the capability defects shown in AD animal models, such as catechin, nobiletin, and alpha-mangostin. Therefore, further investigations exploring a certain bioactive isolate or formulated dosage form and its mechanism of action are necessary to provide effective prevention and supplementary treatment for AD.

PROTECTIVE EFFECT OF SHINGLES VACCINE ON ALZHEIMER’S DISEASE CAN BE MODULATED BY RISK VARIANT OF NECTIN2 GENE

Abstract The aging-related decline in immune surveillance was suggested to play a major role in Alzheimer’s disease (AD). Adult vaccinations may support the aging immune system beyond prevention of the target disease, and through this provide a protection against AD. Such off-target effects of vaccines may potentially be affected by genetic risk factors for AD. To explore this possibility, we estimated association of the vaccination against shingles (reactivated herpes zoster virus infection) received between ages 65-75 with AD onset at ages 75+ in the Health and Retirement Study (HRS) survey participants, comparing the carriers and non-carriers of rs6859 A allele of NECTIN2 gene (AD risk factor that is also involved in vulnerability to viral infections). We used logistic regression model with covariates including sex, race, education, and smoking status. We found that shingles vaccine was significantly associated with lower odds of AD onset later in life, in the total sample (p-value=0.021; OR=0.55 (0.33, 0.92)). After stratification by genotype, the protective effect of vaccine became stronger in rs6859 A carriers (p-value=0.016; OR=0.44 (0.22, 0.86)), but disappeared in the non-carriers, for both significance and size (p-value=0.81; OR=0.90). We conclude that adult shingles vaccine may reduce chances of AD at older ages, and this effect appears more beneficial for carriers of rs6859 A allele of NECTIN2 gene. Repurposing of existing vaccines may benefit the aging immune system, and be a promising approach to personalized genotype-tailored prevention of AD.

FAITH-BASED COMMUNITY OUTREACH TO INCREASE ALZHEIMER’S CLINICAL RESEARCH PARTICIPATION IN THE BLACK COMMUNITY

Abstract Issues: Despite the fact that African Americans are twice more likely to develop Alzheimer’s disease (AD) compared to non-Hispanic whites, they are under-represented in AD clinical research. Lower representation exists in the AHEAD Study as well, which is an AD prevention clinical trial evaluating the efficacy and safety of Lecanemab in 1400 study participants. We sought to raise awareness about AD and increase clinical research participation of African Americans in the AHEAD Study, through a community-based education and recruitment program (CERP). Description: Our diverse team from Eastern Virginia Medical School and Hampton University, a Historically Black College University (HBCU), established a Community Advisory Board and Ministerial Alliance with representation from faith-based, long-standing civic and fraternal organizations within the Greater Hampton Roads Black community. The alliance guided us to identify prioritization areas for addressing sociocultural barriers and increasing clinical research awareness and participation in traditional African American events, key historic community sites, and non-traditional community centers (i.e., YMCA, independent-living, assisted-living centers, Annual Juneteenth Celebration, Black fraternity, and sorority events.) Community health workers, embedded within the community, of the same cultural background and ethnicity, drove our CERP. Lessons Learned: As of July 2023, we offered our program at 45 community events, including community health fairs, civics events, and Purple Sunday luncheons and talks at Black churches in urban and localities in Hampton Roads, in partnership with fraternal and civic community organizations. Out of over 1700 participants, 177 community members have been prescreened for the AHEAD Study.