The Journal of Prevention of Alzheimer's Disease最新文献

{"title":"Association of dietary fatty acids with longitudinal change in plasma-based biomarkers of Alzheimer's disease.","authors":"Serena S Hoost, Lawrence S Honig, Min Suk Kang, Aanya Bahl, Annie J Lee, Danurys Sanchez, Dolly Reyes-Dumeyer, Rafael A Lantigua, Jeffrey L Dage, Adam M Brickman, Jennifer J Manly, Richard Mayeux, Yian Gu","doi":"10.1016/j.tjpad.2025.100117","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100117","url":null,"abstract":"<p><strong>Background: </strong>Elevated intake of omega-3 polyunsaturated fatty acids is linked to a reduced risk of dementia in some prospective studies. However, few studies have examined the relationship between nutrient intake and plasma biomarkers of Alzheimer's disease.</p><p><strong>Objectives: </strong>We explored whether omega-3, omega-6, and monounsaturated fat intakes were associated with changes in plasma biomarkers of Alzheimer's disease over time.</p><p><strong>Design: </strong>The Washington Heights-Inwood Columbia Aging Project is a prospective cohort study (1994-2021); the data set used here includes a mean follow-up of 7.0 years.</p><p><strong>Setting: </strong>Community-based in New York City.</p><p><strong>Participants: </strong>599 dementia-free individuals at baseline who completed a 61-item food frequency questionnaire and had biomarkers measured in plasma from at least two different time points.</p><p><strong>Measurements: </strong>Fatty acid intake tertiles were computed from participant-completed 61-item Willett semi-quantitative food frequency questionnaires (Channing Laboratory, Cambridge, Massachusetts) obtained once at their baseline visit. Plasma-based biomarker assays were performed, using the single molecule array technology Quanterix Simoa HD-X platform, at baseline and follow-up visits. Generalized Estimating Equations (GEE) models were used to evaluate the association between baseline nutrient intake tertile and changes in biomarkers including phospho-tau181, amyloid-beta 42/40 ratio, phospho-tau181/amyloid-beta42 ratio, glial fibrillary acidic protein, neurofilament light chain, and two biomarker patterns derived from Principal Component Analysis (PCA1 and PCA2), with higher scores indicating a high level of neurodegeneration and low level of Alzheimer's disease burden, respectively). Models were adjusted for age, sex, race/ethnicity, education, and calculated total energy intake initially, and additionally for cerebrovascular risk factors.</p><p><strong>Results: </strong>Higher baseline omega-3 intake tertile was associated with lesser decline in PCA2 (β = 0.221, p < 0.001) and amyloid-beta 42/40 ratio (β = 0.022, p = 0.003), and a lesser rise in phospho-tau181 (β = -0.037, p = 0.001). Higher omega-6 intake tertile was linked to a lesser rise in phospho-tau181 (β = -0.050, p < 0.001) and glial fibrillary acidic protein (β = -0.028, p = 0.002). Most associations persisted after adjusting for cardiovascular risk factors.</p><p><strong>Conclusions: </strong>Higher relative baseline intake of omega-3 and omega-6 fatty acids is associated with lesser progression of blood-based biomarkers of Alzheimer's disease. Consuming healthy fatty acids may help prevent accumulation of Alzheimer's disease-related pathological changes.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100117"},"PeriodicalIF":4.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient management pathways in dementia - Resource utilisation, diagnosis and drug treatment in the Stockholm region, Sweden.","authors":"Emil Aho, Dorota Religa, Mozhu Ding, Bengt Winblad, Linus Jönsson, Karin Modig","doi":"10.1016/j.tjpad.2025.100132","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100132","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;New diagnostic and therapeutic options for Alzheimer's disease are beginning to be introduced and expected igto become more widely available in the coming years. Improved understanding of current pathways in diagnosis and initial care of patients with dementia can help inform choices around how best to integrate new technologies in existing care structures.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The aim of this study is to describe the care management pathways defined by the involvement of specialist and primary care for individuals with newly diagnosed dementia. It also seeks to characterise individuals in different management pathways based on resource use prior to diagnosis, the type of dementia diagnosis received, and the proportion who receive symptomatic anti-dementia drug treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Observational cohort study SETTING: Stockholm region, Sweden.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;All newly diagnosed dementia cases between 1st January 2018 to 30th June 2020 (n = 9,781). Dementia diagnoses in primary care were based on Regional Stockholm health care database and diagnoses in specialist care were based on the National Patient Register in Sweden.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Measurements: &lt;/strong&gt;Care management pathways were categorized into three groups: primary care only (diagnosed and followed up in primary care), specialist, no follow-up (diagnosed in specialist care but not followed up in specialist care), and specialist with follow-up (diagnosed and followed up in specialist care). These classifications were based on patients' care episodes from the date of diagnosis and the subsequent 18 months. age at diagnosis, resource utilisation one-year prior diagnosis and diagnosis given and symptomatic anti-dementia treatment 18 months after initial diagnosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 9,781 newly diagnosed dementia cases were identified. In the 18 months following diagnosis, 63 % of patients were diagnosed either partly or fully in specialist care, while 37 % were diagnosed solely in primary care. Patients diagnosed and managed only in primary care were older, spent more days in hospital, and received more social care in the year preceding their diagnosis. Their total care costs were also the highest. Alzheimer's disease was the most common diagnosis (48 %), while 27 % had an unspecified dementia diagnosis, varying by care setting (61 % for patients managed in primary care only and 6 % for patients diagnosed and followed up in specialist care). Overall, 47 % of patients received symptomatic anti-dementia treatment, with the highest share for patients diagnosed and followed up in specialist care (73 %) and the lowest in primary care only (19 %). Diagnosis varied by age and care setting Alzheimer's was most common in settings involving specialist care, whereas unspecified dementia was more common in primary care only regardless of age.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The findings t","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100132"},"PeriodicalIF":4.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain health services for the secondary prevention of cognitive impairment and dementia: Opportunities, challenges, and the business case for existing and future facilities.","authors":"Giovanni B Frisoni, Federica Ribaldi, Gilles Allali, Théophile Bieth, Andrea Brioschi Guevara, Stefano Cappa, Lisa Cipolotti, Kristian Steen Frederiksen, Jean Georges, Frank Jessen, Giacomo Koch, Hugh Masters, Augusto J Mendes, Lutz Frölich, Valentina Garibotto, Oriol Grau-Rivera, Federico E Pozzi, Dorota Religa, Ayda Rostamzadeh, Lenny Shallcross, Susan D Shenkin, Wiesje M van der Flier, Meike W Vernooij, Leonie N C Visser, Jeffrey L Cummings, Philip Scheltens, Bruno Dubois, Elena Moro, Claudio L A Bassetti, Miia Kivipelto","doi":"10.1016/j.tjpad.2025.100098","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100098","url":null,"abstract":"<p><p>A European Task Force has recently developed and published the concept and protocols for the setup of the innovative health offer of Brain Health Services for the secondary prevention of dementia and cognitive impairment (dBHS). dBHS are outpatient health care facilities where adult persons can find an assessment of their risk of developing cognitive impairment and dementia, have their risk level and contributing factors communicated using appropriate language supported by adequate communication tools, can decide to participate to programs for personalized risk reduction if at higher risk, and benefit from cognitive enhancement interventions. This health offer is distinct from that of currently active memory clinics. The ultimate aim of dBHS is to extend healthy life, free from cognitive impairment. Here, we (i) discuss the pertinent opportunities and challenges for those persons who want to benefit from dBHS, professionals, and wider society, (ii) describe the concepts, protocols, organizational features, and patient journeys of some currently active dBHS in Europe, and (iii) argue in favor of the business case for dBHS in Europe.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100098"},"PeriodicalIF":4.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain health PRO/Santé cerveau PRO: The development of a web-based program for dementia literacy and risk factor reduction.","authors":"Sylvie Belleville, Nicole D Anderson, Louis Bherer, Richard Camicioli, Julie Carrier, Senny Chan, Marc Cuesta, Thien Thanh Dang-Vu, Emily Dwosh, Alexandra J Fiocco, Guylaine Ferland, Brigitte Gilbert, Elaine Harris, Inbal Itzhak, Pamela Jarrett, Mohamed Abdelhafid Kadri, Danielle Laurin, Teresa Liu-Ambrose, Chris A McGibbon, Laura Middleton, Lesley Miller, Haakon B Nygaard, Manuel Montero-Odasso, Kelly Murphy, Natalie Phillips, M Kathleen Pichora-Fuller, Julie M Robillard, Eric E Smith, Mark Speechley, Amal Trigui, Walter Wittich, Howard Chertkow, Howard H Feldman","doi":"10.1016/j.tjpad.2025.100134","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100134","url":null,"abstract":"<p><strong>Background: </strong>Online educational programs focused on ways to improve brain health could increase participant literacy, empowerment, and engagement in activities that support personal brain health, potentially reducing dementia risk.</p><p><strong>Objectives: </strong>Our goal was to develop an evidence-based online educational program with a focus on risk and protective factors for dementia. Here we present the rationale and features of the program and include results from a pilot study that assessed usability and acceptability.</p><p><strong>Design: </strong>This project is part of the Can-Thumbs UP (CTU) initiative. An Intervention Mapping Approach framework and co-construction approach was used to develop the online program. A pre-post pilot open label design was used to test the usability and acceptance of this at-home educational program.</p><p><strong>Setting: </strong>The program and assessment for the pilot study were delivered fully remotely.</p><p><strong>Participants: </strong>Twenty community-dwelling older adults (60-83 years of age, 65 % female) living in Canada who were at increased risk of dementia.</p><p><strong>Program: </strong>The Brain Health PRO/Santé Cerveau PRO is a web-based 45-week program available in French and English. It provides general information and guidance on seven modifiable risk factors for dementia: physical activity, nutrition, cognitively stimulating activities, sleep, social and psychological health, vascular health, and vision/hearing. After completing a brief intake questionnaire, users are provided with an individualized risk profile to personalize priorities and goals. During the course of the program, users receive feedback on lifestyle changes. For this pilot study, participants completed a 15-week version of the program.</p><p><strong>Measurements: </strong>This pilot study reports measures of usability (System Usability Scale), acceptance (Technology Acceptance Model-2) as well as risk profiles at intake based on self-reported questionnaires.</p><p><strong>Results: </strong>Two logic models were developed to identify the determinants of risk for dementia and how these could be targeted by the program. A review of dementia risk and protective factors and online educational programs for older adults, as well as co-creation activities with experts, stakeholders, and citizen advisors, were used to identify the determinants, target, format, and content of the program. The pilot study reports excellent usability and acceptance with scores of 80.4/100 and 93.5/120 respectively.</p><p><strong>Conclusion: </strong>Intervention mapping and co-construction approaches facilitated the design of a program that effectively balances the delivery of scientific content with the specific constraints, needs and abilities of older adults.</p><p><strong>Trial registration: </strong>NCT05347966.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100134"},"PeriodicalIF":4.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary patterns and blood-based biomarkers of Alzheimer's disease in cognitively intact older adults: Findings from a population-based study.","authors":"Anja Mrhar, Adrián Carballo-Casla, Giulia Grande, Martina Valletta, Claudia Fredolini, Laura Fratiglioni, Milica Gregorič Kramberger, Aleš Kuhar, Bengt Winblad, Amaia Calderón-Larrañaga, Davide Liborio Vetrano","doi":"10.1016/j.tjpad.2025.100124","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100124","url":null,"abstract":"<p><strong>Background: </strong>Diet can impact cognitive aging, but comprehensive data from human studies is lacking and the underlying biological mechanisms are still not fully understood.</p><p><strong>Objectives: </strong>To investigate the associations between two dietary patterns consistently linked to inflammation and brain health [the Mediterranean diet (MDS) and inflammatory potential of diet (EDII)] and five blood-based biomarkers of Alzheimer´s disease (AD) in a sample of dementia-free community-dwelling older adults.</p><p><strong>Design and setting: </strong>We used cross-sectional data from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K).</p><p><strong>Participants: </strong>Participants who were institutionalized, had dementia or Parkinson's disease, or had missing data on diet and/or biomarkers were excluded. Our study sample consisted of 1907 adults ≥60 years old.</p><p><strong>Measurements: </strong>Adherence to the MDS and EDII was assessed using a validated food frequency questionnaire. T-tau, p-tau181, Aβ 42/40, NfL, and GFAP were measured in serum. Associations were estimated through quantile regression models at the 25th, 50th, and 75th percentiles of the biomarkers' levels, and were adjusted for potential confounders and stratified by sex, age, and APOE-e4 genotype.</p><p><strong>Results: </strong>In the whole sample, higher adherence to the MDS was associated with lower levels of p-tau181 at the 50th and 75th percentiles [β (95% CI) per 1-SD increment = -0.028 (-0.053, -0.002) and -0.036 (-0.072, -0.001), respectively], while higher adherence to the EDII was associated with higher levels of NfL at the 75th percentile [β (95% CI) per 1-SD increment =0.031 (0.008, 0.053)]. Associations with other biomarkers were only apparent at lower levels of their distribution. Subgroup analyses showed: 1) a stronger inverse association between the MDS and p-tau181 in APOE-e4 carriers than non-carriers, and 2) an inverse association of the MDS with GFAP only in participants ≥78 years.</p><p><strong>Conclusions: </strong>Diet seems to be associated with biomarkers of AD pathology in cognitively intact older adults. Some associations were more apparent in the presence of genetic predisposition for AD or advanced age.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100124"},"PeriodicalIF":4.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifestyle factors and plasma biomarkers of Alzheimer's disease: A narrative review.","authors":"Claudie Hooper, Nicola Coley, Julien Delrieu, Sophie Guyonnet","doi":"10.1016/j.tjpad.2025.100130","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100130","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder characterised by amyloid-β (Aβ), tau hyperphosphorylation and neurodegeneration. Blood-based biomarkers are emerging as a minimally invasive tool for disease detection and monitoring. This review depicts the relationships between modifiable lifestyle factors (nutrition, physical activity (PA), sleep, alcohol consumption, smoking, and social isolation) and plasma biomarkers of AD: Aβ₄₂, Aβ₄₀, Aβ_42/40, phosphorylated tau, total tau, neurofilament light chain (NfL) and glial fibrillary acidic protein. Limited evidence suggests that better nutrition is associated with favourable AD plasma biomarker profiles and that PA is associated with less plasma NfL and Aβ, whilst poor sleep is associated with elevated plasma Aβ. However, lack of data and inconsistent findings highlight the need for further investigation to substantiate or refute these trends. Moreover, future research should include the analysis of lifestyle on plasma biomarkers according to gender, metabolic health and APOE status. Considering the growing emphasis on modifiable lifestyle factors for preventing and delaying dementia onset further investigation is justified.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100130"},"PeriodicalIF":4.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"17th Clinical Trials on Alzheimer's Disease (CTAD) Madrid, Spain, October 29 - November 1, 2024: Symposia, Oral Communications\" [J Prev Alzheimers Dis 2025;12(1S):100043].","authors":"","doi":"10.1016/j.tjpad.2025.100120","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100120","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100120"},"PeriodicalIF":4.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current status and future directions for the diagnosis and management of mild cognitive impairment in Southeast Asia: A SEACURE consensus paper.","authors":"Gursimar Bhalla, Pricilia Tanoto, Ashwati Vipin, Xiao Yuan James Chen, Yi Jin Leow, Christopher Chen, Philip Lin Kiat Yap, Reshma A Merchant, Saima Hilal, Anam Paulus Ong, Encarnita Raya Ampil, Mohamad Imran Idris, Irene Looi, Jacqueline Dominguez, Suraya Yusoff, Maw Pin Tan, Cong Thang Tran, Mai Trang Tong, Vorapun Senanarong, Yuda Turana, Nagaendran Kandiah","doi":"10.1016/j.tjpad.2025.100110","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100110","url":null,"abstract":"<p><p>Global aging populations are facing increased prevalence of mild cognitive impairment (MCI) - the preclinical stage of dementia characterized by single/multi-domain neurocognitive decline that does not impair an individual's normal daily functioning. Asian populations are at increased risk of developing MCI and dementia, and many cases go undetected in Southeast Asia (SEA), resulting in increased burden on patients, caregivers and national healthcare systems. There is an urgent need for efficient and scalable diagnostic and management strategies across SEA. Our findings illustrate that current strategies are limited by insufficient resources and a lack of awareness, particularly in developing SEA nations. Strategies for improving the MCI landscape in SEA include increasing widespread community awareness and cognitive health screenings for individuals with a history of vascular risk factors, validation of traditional cognitive screening tests in the respective countries, greater access to blood-biomarker testing, and the development and validation of novel digitized diagnostics.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100110"},"PeriodicalIF":4.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis of druggable genes to facilitate Alzheimer's disease therapy: A multi-cohort machine learning study.","authors":"Jichang Hu, Yong Luo, Xiaochuan Wang","doi":"10.1016/j.tjpad.2025.100128","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100128","url":null,"abstract":"<p><strong>Background: </strong>The swift rise in the prevalence of Alzheimer's disease (AD) alongside its significant societal and economic impact has created a pressing demand for effective interventions and treatments. However, there are no available treatments that can modify the progression of the disease.</p><p><strong>Methods: </strong>Eight AD brain tissues datasets and three blood datasets were obtained. Consensus clustering was utilized as a method to discern the various subtypes of AD. Then, module genes were screened using weighted correlation network analysis (WGCNA). Furthermore, screening hub genes was conducted through machine-learning analyses. Finally, A comprehensive analysis using a systematic approach to druggable genome-wide Mendelian randomization (MR) was conducted.</p><p><strong>Results: </strong>Two AD subclasses were identified, namely cluster.A and cluster.B. The levels of gamma secretase activity, beta secretase activity, and amyloid-beta 42 were found to be significantly elevated in patients classified within cluster A when compared to those in cluster B. Furthermore, by utilizing the differentially expressed genes shared among these clusters, along with identifying druggable genes and applying WGCNA to these subtypes, we were able to develop a scoring system referred to as DG.score. This scoring system has demonstrated remarkable predictive capability for AD when evaluated against multiple datasets. Besides, A total of 30 distinct genes that may serve as potential drug targets for AD were identified across at least one of the datasets investigated, whether derived from brain samples or blood analyses. Among the identified genes, three specific candidates that are considered druggable (LIMK2, MAPK8, and NDUFV2) demonstrated significant expression levels in both blood and brain tissues. Furthermore, our research also revealed a potential association between the levels of LIMK2 and concentrations of CSF Aβ (OR 1.526 (1.155-2.018)), CSF p-tau (OR 1.106 (1.024-01.196)), and hippocampal size (OR 0.831 (0.702-0.948)).</p><p><strong>Conclusions: </strong>This study provides a notable advancement to the existing literature by offering genetic evidence that underscores the potential therapeutic advantages of focusing on the druggable gene LIMK2 in the treatment of AD. This insight not only contributes to our understanding of AD but also guides future drug discovery efforts.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100128"},"PeriodicalIF":4.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: Enhancing Statin Research for Alzheimer's Prevention: Suggestions for Future Studies and Policy Implications.","authors":"Zirong Ye, Jiahe Deng, Xiuxia Wu, Jingwen Cai, Sicheng Li, Xiaochun Chen, Jiawei Xin","doi":"10.1016/j.tjpad.2025.100119","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100119","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100119"},"PeriodicalIF":4.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}