Christopher Chen, Sadao Katayama, Jae-Hong Lee, Jun-Young Lee, Masaki Nakagawa, Kentaro Torii, Tomoo Ogawa, Amitabh Dash, Michael Irizarry, Shobha Dhadda, Michio Kanekiyo, Steve Hersch, Takeshi Iwatsubo
{"title":"Clarity AD: Asian regional analysis of a phase III trial of lecanemab in early Alzheimer's disease.","authors":"Christopher Chen, Sadao Katayama, Jae-Hong Lee, Jun-Young Lee, Masaki Nakagawa, Kentaro Torii, Tomoo Ogawa, Amitabh Dash, Michael Irizarry, Shobha Dhadda, Michio Kanekiyo, Steve Hersch, Takeshi Iwatsubo","doi":"10.1016/j.tjpad.2025.100160","DOIUrl":"10.1016/j.tjpad.2025.100160","url":null,"abstract":"<p><strong>Background: </strong>Across Asia, Alzheimer's disease prevalence is expected to rise dramatically due to, among other factors, rapidly aging populations. Alzheimer's disease pathology is triggered by the accumulation of soluble and insoluble aggregated Aβ peptides (oligomers, protofibrils, and fibrils). Lecanemab is a recently approved humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated Aβ species (oligomers, protofibrils), with activity at insoluble fibrils. In the recent 18-month phase 3 Clarity AD study, lecanemab demonstrated a consistent slowing of decline in clinical (global, cognitive, functional, and quality of life) outcomes, and reduction in brain amyloid in early Alzheimer's disease. Lecanemab was well tolerated in Clarity AD, with an increase in incidence of infusion related reactions and amyloid-related imaging abnormalities (ARIA) versus placebo.</p><p><strong>Objectives: </strong>The objective of this manuscript is to present the results for the Asian region population of Clarity AD.</p><p><strong>Design: </strong>The core Clarity AD study was an 18-month, multicenter, double-blind, placebo-controlled, parallel-group study.</p><p><strong>Setting: </strong>Academic and clinical centers in Asia PARTICIPANTS: A total of 294 individuals with early Alzheimer's disease (i.e., mild cognitive impairment or mild Alzheimer's disease).</p><p><strong>Intervention: </strong>Eligible patients were randomized across 2 treatment groups (placebo and lecanemab 10 mg/kg biweekly) according to a fixed 1:1 schedule.</p><p><strong>Measurements: </strong>The primary efficacy endpoint in the core study was change in the Clinical Dementia Rating-Sum-of-Boxes (CDR-SB) from baseline at 18 months. Key secondary endpoints included change from baseline at 18 months in amyloid PET Centiloids (in patients participating in the amyloid PET sub-study), AD COMposite Score (ADCOMS) and AD Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14). Safety was monitored throughout the study in a blinded manner by the sponsor and in an unblinded manner by an independent data safety monitoring committee.</p><p><strong>Results: </strong>Of the total of 1795 subjects randomized in Clarity AD, 294 subjects were in the Asian region (Japan:152; Korea:129; Singapore:13). The efficacy of lecanemab was consistent with the overall population. For the primary endpoint, there was a slowing of decline with lecanemab in the CDR-SB at 18 months compared to placebo in the Asian region (adjusted mean difference: -0.349; 95 % confidence intervals: -0.773, 0.076; 24 % slowing of decline). Results for the secondary efficacy endpoints also favored lecanemab versus placebo in Asians. Lecanemab was well tolerated in Asian subjects, with a safety profile in Asian subjects similar to the overall Clarity AD population. The most common adverse events of special interest were ARIA-H (lecanemab:14.4 %; placebo:16.2 %), ARIA-E (lecanemab:6.2 %; placebo:1.4 %), and in","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100160"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796568","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":"Comparative efficacy and safety of antidiabetic agents in Alzheimer's disease: A network meta-analysis of randomized controlled trials.","authors":"Zixin Cai, Jiaxin Zhong, Guanghui Zhu, Jingjing Zhang","doi":"10.1016/j.tjpad.2025.100111","DOIUrl":"10.1016/j.tjpad.2025.100111","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatment options. Emerging evidence suggests that antidiabetic agents may offer neuroprotective effects by targeting shared pathophysiological mechanisms such as insulin resistance and neuroinflammation. However, the comparative efficacy, and safety of these agents in the treatment of AD remain unclear.</p><p><strong>Objectives: </strong>This study aimed to systematically evaluate and compare the efficacy and safety of antidiabetic agents for improving cognitive outcomes, reducing amyloid-β (Aβ) deposition, and managing adverse effects in patients with AD, using a network meta-analysis of randomized controlled trials (RCTs).</p><p><strong>Methods: </strong>A comprehensive literature search was conducted across multiple databases to identify RCTs examining the effects of antidiabetic agents in patients with AD. The primary outcomes included cognitive performance (e.g., MMSE scores), Aβ deposition (measured via CSF biomarkers), and safety/adverse effects. A network meta-analysis was performed to integrate direct and indirect evidence, ranking interventions using Surface Under the Cumulative Ranking (SUCRA) probabilities. Risk of bias was assessed using the Cochrane risk-of-bias tool.</p><p><strong>Results: </strong>A total of 26 studies, involving 7,361 participants, were included in the analysis. The interventions evaluated included insulin detemir (both low-dose and high-dose), liraglutide, exenatide, metformin, and pioglitazone. Both low-dose insulin detemir (mean difference: 2.10, 95 % CI: 1.04 to 3.15), high-dose insulin detemir (mean difference: 1.40, 95 % CI: -0.07 to 2.88), exenatide (mean difference: 1.19, 95 % CI: 0.06 to 2.32), and metformin combined with exenatide (mean difference: 1.06, 95 % CI: -1.68 to 3.80) showed cognitive improvements compared to placebo. Among these, low-dose insulin detemir demonstrated the most significant improvement. In terms of reducing Aβ deposition, metformin ranked highest in effectiveness, with the highest SUCRA score (84.6), followed by high-dose insulin detemir (SUCRA: 54.1). Low-dose insulin detemir (SUCRA: 51.1) also demonstrated moderate efficacy. Low-dose insulin detemir showed some reduction in Aβ deposition (mean difference: -0.31, 95 % CI: -2.82 to 2.20), although statistical significance was limited. Liraglutide exhibited the highest rate of study treatment withdrawal (mean difference: 1.97, 95 % CI: -0.07 to 4.00), while pioglitazone demonstrated the lowest withdrawal rates (mean difference: 0.07, 95 % CI: -0.03 to 0.17).</p><p><strong>Conclusions: </strong>This network meta-analysis provides valuable insights into the comparative efficacy and safety of antidiabetic agents in AD. Low-dose insulin detemir demonstrated the most significant cognitive improvement and a moderate effect on reducing Aβ deposition. Metformin emerged as the most effective agent for reducing Aβ levels, thou","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100111"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537549","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}
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
{"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":"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":"2025-05-01","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":"Multisensory stimulation reduces neuropsychiatric symptoms and enhances cognitive function in older adults with dementia: A meta-analysis of randomized controlled trials.","authors":"Tiara Octary, Melati Fajarini, Hidayat Arifin, Ruey Chen, Chien-Mei Sung, Li-Fang Chang, Chia-Hui Wang, Kondwani Joseph Banda, Kuei-Ru Chou","doi":"10.1016/j.tjpad.2025.100091","DOIUrl":"10.1016/j.tjpad.2025.100091","url":null,"abstract":"<p><strong>Objective: </strong>Multisensory stimulation defined as engaging multiple senses (visual, olfactory, auditory, gustatory, and tactile), has been demonstrated to improve older adults' general health. However, its effectiveness in mitigating neuropsychiatric symptoms (NPSs) and cognitive deficits in older adults with dementia remains unclear. This meta-analysis evaluated the efficacy of multisensory stimulation in ameliorating NPSs and improving overall cognitive function in older adults with dementia.</p><p><strong>Methods: </strong>We searched eight databases to September 2024 without restriction. Older adults with all stages of dementia aged 65 years and above were included. To estimate the pooled effect size, Hedge's g (g) values were calculated using a random-effects model. Heterogeneity was assessed using the Q, I², and τ² statistics. Subgroup and meta-regression analyses were performed to identify moderators. Publication bias was assessed using Begg and Mazumdar's rank correlation and Egger's linear regression tests.</p><p><strong>Results: </strong>This review included 16 studies (974 patients). Multisensory stimulation significantly reduced agitation (g= -0.96; 95 %CI= -1.44, -0.48), apathy (g= -1.27; 95 %CI= -2.08, -0.46), and depression (g= -0.28; 95 %CI= -0.48, -0.07). Moreover, the intervention significantly improved overall cognitive function (g= 0.30; 95 %CI= 0.09, 0.52). However, multisensory stimulation had no significant effect on anxiety (g= -0.81; 95 %CI= -1.79, 0.17). Significant heterogeneity was observed in agitation, apathy, and anxiety. Moreover, meta-regression analyses by educational level (junior high school and above) revealed significant moderators in agitation.</p><p><strong>Conclusions: </strong>Multisensory stimulation shows promise as a non-pharmacological intervention for older adults with dementia. It may effectively mitigate NPSs and improve cognitive function into clinical practice as an alternative therapeutic.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100091"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477035","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":"The associations between fresh vegetable and fruit consumption and plasma and PET biomarkers in preclinical Alzheimer's disease: A cross-sectional and longitudinal study of Chinese population.","authors":"Heling Chu, Chuyi Huang, Fang Xie, Qihao Guo","doi":"10.1016/j.tjpad.2025.100076","DOIUrl":"10.1016/j.tjpad.2025.100076","url":null,"abstract":"<p><strong>Background: </strong>The identification of the modifiable lifestyle factors including dietary habits in older adults of preclinical Alzheimer's disease (AD) and early effective interventions are of great importance.</p><p><strong>Objectives: </strong>We studied whether the consumption of fresh vegetables and fruits was different between cognitively unimpaired (CU) and cognitively impaired (CI) population and mainly investigated the associations between vegetable and fruit consumption and PET and plasma AD biomarkers in older CU adults with higher β-amyloid (Aβ) burden.</p><p><strong>Design, setting, and participants: </strong>Older adults with the age of 50-85 years were enrolled for a cross-sectional and longitudinal study. The groups depended on whether the participants were CU or CI. Partial participants whose habits remained unchanged were followed up.</p><p><strong>Measurements: </strong>The consumption data of vegetables and fruits were collected using a validated self-reported questionnaire. We mainly investigated the associations between vegetable and fruit consumption and various biomarkers in CU participants with positive <sup>18</sup>F-florbetapir PET scan (Aβ-PET), part of whom also underwent plasma AD biomarkers tests and <sup>18</sup>F-MK6240 PET scan (tau-PET). Correlation and multiple linear regression analyses were used to investigate the associations between vegetable and fruit consumption and AD biomarkers.</p><p><strong>Results: </strong>A total of 1433 participants were enrolled, of which CU accounted for 49.4 %. Most of the intake habits of vegetables and fruits was different between CU and CI participants. 177 CU participants with Aβ-PET positive were selected for the following study. Multiple linear regression analysis showed higher consumption of fresh vegetables (>200 g/d), dark vegetables (>100 g/d, ≥2d/week), fruits (>100 g/d), berries (>100 g/d) and grapes (>100 g/d) more or less had associations with the plasma biomarkers including Aβ40, t-Tau, p-Tau-181 and neurofilament light chain as well as amyloid and Tau PET biomarkers. Most of the habits were associated with the change of cognitive function after an approximately two-year follow-up. Especially, higher intakes of fruits and grapes correlated with both lower Aβ and Tau burden and inversely with cognitive decline after follow-up.</p><p><strong>Conclusion: </strong>Our data indicates that higher consumption of vegetables, dark vegetables, fruits, berries and grapes is associated with amyloid and Tau PET and plasma biomarkers in preclinical AD participants and the changes of cognitive function after follow-up. Higher intakes of fruits (>100 g/d) and grapes (>100 g/d) may be more helpful for reducing the risk of AD development.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100076"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075546","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}
Elina Pietilä, Eliisa Löyttyniemi, Seppo Koskinen, Jenni Lehtisalo, Matti Viitanen, Juha O Rinne, Antti Jula, Laura L Ekblad
{"title":"Corrigendum to Enhancing dementia prediction: A 19-year validation of the CAIDE risk score with insulin resistance and APOE ε4 integration in a population-based cohort.","authors":"Elina Pietilä, Eliisa Löyttyniemi, Seppo Koskinen, Jenni Lehtisalo, Matti Viitanen, Juha O Rinne, Antti Jula, Laura L Ekblad","doi":"10.1016/j.tjpad.2025.100158","DOIUrl":"10.1016/j.tjpad.2025.100158","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100158"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773268","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}
L Waterink, S J van der Lee, D Nijland, F I van der Zee, L N C Visser, Y A L Pijnenburg, S A M Sikkes, W M van der Flier, M D Zwan
{"title":"Feasibility and acceptability of remote APOE-genotyping among research volunteers of an online recruitment registry (The Dutch Brain Research Registry).","authors":"L Waterink, S J van der Lee, D Nijland, F I van der Zee, L N C Visser, Y A L Pijnenburg, S A M Sikkes, W M van der Flier, M D Zwan","doi":"10.1016/j.tjpad.2025.100099","DOIUrl":"10.1016/j.tjpad.2025.100099","url":null,"abstract":"<p><strong>Background: </strong>Participant recruitment for preclinical Alzheimer's disease (AD) prevention studies is challenging. Online registries facilitate large scale prescreening of individuals at risk for AD to accelerate recruitment. APOE-prescreening has the potential to better identify at-risk individuals. This study investigated the feasibility and acceptability of at-home APOE-genotyping in cognitively-normal registrants of an online registry.</p><p><strong>Methods: </strong>We invited 9,287 cognitively-normal registrants of Dutch Brain Research Registry (DBRR) aged 50 to 75 for at-home APOE-genotype testing, without receiving the results. Feasibility was measured by participation ratio (participation/interested), swab-return ratio (returned-swabs/participation), and genotyping-success ratio (analyzed swabs/returned swabs). Acceptability was measured with online questions about information provision and project scope. We explored prescreening questions potentially reducing screen-failures.</p><p><strong>Results: </strong>Feasibility was high with an 0.89 participation ratio (2,886/3,251), 0.90 swab-return ratio (2,886/2,597), 0.99 genotyping-success ratio (2,558/2,597). Acceptability was high, as participants were content with the information provision (87 %-97 %, n= 1,709-1,894), which was also well understood (91 %-93 %, n = 1,772-1,802). Among successful-analyzed swabs (n = 2,558), 27 % participants were APOE-ε4 heterozygote (n = 703), and 2 % homozygote (n = 60). Prescreening on a positive family history leads to a third reduction in the number of invitations needed to identify one APOE-ε4 carrier.</p><p><strong>Conclusion: </strong>Our results suggest that APOE-ɛ4 genotyping in participants of an online research registry is feasible, well received and could be used to prescreen individuals at risk for AD for prevention studies. Adding a positive family history before invitation for APOE-genotyping, would further improve the prescreening process and reduce screen failures when identifying carriers.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100099"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504036","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":"Are Appropriate Use Recommendations useful in clinical practice?","authors":"Serge Gauthier","doi":"10.1016/j.tjpad.2025.100165","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100165","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 5","pages":"100165"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054975","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":"Value of blood neural cell-derived small extracellular vesicles in the diagnosis and prediction of Alzheimer's disease: A systematic review","authors":"Weibing Pan, Yu Teng, Xiaowan Han, Shaojiao Liu, Xingxue Pang, Lei Wang, Mingjing Zhao","doi":"10.1016/j.tjpad.2025.100193","DOIUrl":"10.1016/j.tjpad.2025.100193","url":null,"abstract":"<p><p>Blood neural cell-derived small extracellular vesicles (sEVs) can directly reflect changes in brain tissue and are easier to obtain than cerebrospinal fluid. This article systematically reviews the alterations of proteins and miRNAs from neural cell-derived sEVs in patients with Alzheimer's disease (AD), and summarizes the biomarkers with clinical diagnostic and predictive value. PubMed, Web of Science, Embase, and Cochrane Library were searched for studies in blood neural cell-derived sEVs in AD patients up to May 2024. According to the inclusion and exclusion criteria, the literature was screened, the information was extracted and the quality was evaluated. Proteins and miRNAs from neural cell-derived sEVs were classified and summarized, focusing on target molecules with high diagnostic and predictive values for AD. A final 34 articles reporting 5601 participants were included. In cross-sectional studies, Aβ- and Tau-related proteins (Aβ42, Aβ42/40, p-S396-Tau, p-Tau181), p-S312-IRS-1, and cathepsin D were increased, conversely, synaptic proteins (neurogranin, synaptotagmin, synaptophysin, synaptopodin, NMDAR2A) and REST were decreased in blood neuron-derived sEVs (NDsEVs) of patients with AD. While miR-29c-3p was increased in blood NDsEVs and glial cell-derived sEVs. Each of these proteins and miRNAs demonstrated high AD diagnostic value. Additionally, blood astrocyte-derived sEVs (ADsEVs) showed increased complement effector proteins and decreased complement regulatory proteins with a moderate diagnostic value. In longitudinal cohort studies, three composite models displayed high predictive efficacy for early AD prediction, and could predict the occurrence of AD within 1-10 years. Therefore, Aβ- and Tau-related proteins, synaptic proteins, and miRNA in blood neural cell-derived sEVs demonstrate high AD diagnostic and predictive values serving as important biomarkers. Especially, synaptic proteins showed significant changes in the early clinical stage, which has early predictive value.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100193"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054974","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":"Rebuttal letter on behalf of all authors in response to the Letter to the Editor.","authors":"Marwan Noel Sabbagh","doi":"10.1016/j.tjpad.2025.100136","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100136","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 5","pages":"100136"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000464","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}