Alzheimer's & Dementia最新文献

{"title":"Distinct patterns of cognitive traits in extreme old age and Alzheimer's disease","authors":"Yoshinori Nishimoto,&nbsp;Takashi Sasaki,&nbsp;Yukiko Abe,&nbsp;Norikazu Hara,&nbsp;Akinori Miyashita,&nbsp;Mika Konishi,&nbsp;Yoko Eguchi,&nbsp;Daisuke Ito,&nbsp;Nobuyoshi Hirose,&nbsp;Masaru Mimura,&nbsp;Japanese Alzheimer's Disease Neuroimaging Initiative,&nbsp;Takeshi Ikeuchi,&nbsp;Hideyuki Okano,&nbsp;Yasumichi Arai","doi":"10.1002/alz.70155","DOIUrl":"https://doi.org/10.1002/alz.70155","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Clinical features of cognitive performance in extreme old age differ from those of pathological cognitive decline in Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We compared cognitive traits between 638 centenarians aged 100–115 years and 208 and 221 patients with AD from independent facilities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The presence of the apolipoprotein E (<i>APOE)</i> ε4 allele did not affect Mini-Mental State Examination (MMSE) scores in centenarians. Centenarians retained the ability to follow three consecutive commands, associated with their educational background and activities of daily living. Cognitive retention remained unchanged in semi-supercentenarians (aged ≥ 105 years) and supercentenarians (aged ≥110 years). A quantitative genome-wide association study (GWAS) identified two loci associated with maintaining the ability to follow three consecutive commands.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This is the first study to compare cognitive traits between &gt;600 centenarians and patients with AD. Centenarians attained higher MMSE scores for the phenotype of following three consecutive commands than patients with AD, being useful in clinical practice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Cognitive phenotypes in centenarians differ from those in the AD groups</li>\u0000 \u0000 <li>Clinical trait to follow consecutive instructions is retained in centenarians but not in AD groups</li>\u0000 \u0000 <li>GWAS identified SNPs related to the maintained trait of MMSE in centenarians</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Healthy lifestyle factors outweigh influence of APOE genetic risk on extending cognitively healthy life expectancy among Chinese older adults: evidence from a nationwide cohort study","authors":"Longbing Ren,&nbsp;Fan Hu,&nbsp;Sebastian Walsh,&nbsp;Xurui Jin,&nbsp;Yang Hu,&nbsp;Shaojie Li,&nbsp;Yuling Jiang,&nbsp;Mingzhi Yu,&nbsp;Yifei Wu,&nbsp;Grace Yuange Zang,&nbsp;Keyang Liu,&nbsp;Huashuai Chen,&nbsp;Jing Sun,&nbsp;Yan Zhang,&nbsp;Kokoro Shirai,&nbsp;Yi Zeng,&nbsp;Quincy M. Samus,&nbsp;Gill Livingston,&nbsp;Yao Yao","doi":"10.1002/alz.70090","DOIUrl":"https://doi.org/10.1002/alz.70090","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Understanding the interplay between genetic factors and lifestyle choices in cognitive health is crucial for enhancing late-life quality. This study examines the effects of Apolipoprotein E (APOE) genotypes and healthy lifestyles on life expectancy with and without cognitive impairment (CI) in Chinese older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Data from 6488 participants aged at least 65 in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed using continuous-time three-state Markov models. Cognitive function was assessed with the Mini-Mental State Examination (MMSE).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>APOE ε4 allele carriers had a higher risk of transitioning from cognitively healthy (CH) to impaired, while ε2 carriers had a reduced risk of transitioning from healthy to death. Participants with 4 or 5 healthy lifestyle factors experienced significant protective effects, extending the cognitively healthy life expectancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings underscore the importance of promoting healthy lifestyles to delay cognitive decline, regardless of genetic predispositions, particularly in the Asian context.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Compared with ε3 homozygotes, APOE ε4 carriers in China have a higher risk of transitioning from CH to CI, and APOE ε2 carriers with CH have a lower risk of transitioning to death.</li>\u0000 \u0000 <li>Healthy lifestyles can extend life expectancy, primarily extending CH life expectancy.</li>\u0000 \u0000 <li>Healthy lifestyles reduce the risk of CI and delay its onset in later life, regardless of APOE genetic risk.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood-based biomarkers for Alzheimer's disease in Down syndrome: A systematic review and meta-analysis","authors":"Yajing Zhou,&nbsp;Rory Sheehan,&nbsp;Lizhi Guo,&nbsp;Andre Strydom","doi":"10.1002/alz.70135","DOIUrl":"https://doi.org/10.1002/alz.70135","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Individuals with Down syndrome (DS) are at high risk of Alzheimer's disease (AD), displaying AD pathology similar to the general population. This study evaluated AD-related blood biomarkers in DS within the AT(N) framework through a systematic review and meta-analysis of studies published between 2017 and October 2024. The meta-analysis focused on plasma amyloid beta (Aβ)42, Aβ40, total tau (t-tau), phosphorylated tau (p-tau)181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) levels, comparing 2109 DS individuals and 1006 euploid controls. Plasma Aβ42, Aβ40, NfL, and GFAP levels were significantly elevated in DS compared to euploid controls, while the Aβ42/40 ratio was reduced. In DS-AD individuals, Aβ42 and t-tau levels were elevated, with p-tau181, NfL, and GFAP consistently high across clinical subgroups. Notably, Aβ40 and the Aβ42/40 ratio changed significantly in preclinical AD, while t-tau increased in clinical AD. Incorporating inflammation (I) markers highlights neuroinflammation's role in DS-AD progression, supporting the blood-based AT(N)I framework for early AD detection and monitoring in DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We reviewed 58 studies on Down syndrome (DS) blood biomarkers and a meta-analysis of 18 using single molecule array.</li>\u0000 \u0000 <li>Plasma amyloid beta (Aβ)42, Aβ40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) levels were elevated in DS compared to controls.</li>\u0000 \u0000 <li>DS-Alzheimer's disease (AD) individuals showed higher Aβ42, total tau (t-tau), phosphorylated tau (p-tau)181, NfL, and GFAP levels.</li>\u0000 \u0000 <li>Plasma p-tau181, NfL, and GFAP were elevated across all clinical subgroups.</li>\u0000 \u0000 <li>Aβ40 and Aβ42/40 ratio changed in preclinical AD; t-tau rose in clinical AD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Federated learning with multi-cohort real-world data for predicting the progression from mild cognitive impairment to Alzheimer's disease","authors":"Jinqian Pan,&nbsp;Zhengkang Fan,&nbsp;Glenn E. Smith,&nbsp;Yi Guo,&nbsp;Jiang Bian,&nbsp;Jie Xu","doi":"10.1002/alz.70128","DOIUrl":"https://doi.org/10.1002/alz.70128","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Leveraging routinely collected electronic health records (EHRs) from multiple health-care institutions, this approach aims to assess the feasibility of using federated learning (FL) to predict the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We analyzed EHR data from the OneFlorida+ consortium, simulating six sites, and used a long short-term memory (LSTM) model with a federated averaging (FedAvg) algorithm. A personalized FL approach was used to address between-site heterogeneity. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) and feature importance techniques.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Of 44,899 MCI patients, 6391 progressed to AD. FL models achieved a 6% improvement in AUC compared to local models. Key predictive features included body mass index, vitamin B12, blood pressure, and others.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>FL showed promise in predicting AD progression by integrating heterogeneous data across multiple institutions while preserving privacy. Despite limitations, it offers potential for future clinical applications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We applied long short-term memory and federated learning (FL) to predict mild cognitive impairment to Alzheimer's disease progression using electronic health record data from multiple institutions.</li>\u0000 \u0000 <li>FL improved prediction performance, with a 6% increase in area under the receiver operating characteristic curve compared to local models.</li>\u0000 \u0000 <li>We identified key predictive features, such as body mass index, vitamin B12, and blood pressure.</li>\u0000 \u0000 <li>FL shows effectiveness in handling data heterogeneity across multiple sites while ensuring data privacy.</li>\u0000 \u0000 <li>Personalized and pooled FL models generally performed better than global and local models.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changing definitions of disease: Transformations in the diagnostic criteria for Alzheimer's disease","authors":"Lennart H. van der Molen,&nbsp;Marianne Boenink,&nbsp;Harro van Lente,&nbsp;Edo Richard","doi":"10.1002/alz.70133","DOIUrl":"https://doi.org/10.1002/alz.70133","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Whether Alzheimer's disease (AD) should be defined by symptoms, biological processes, or both, is a matter of debate. We aim to reconstruct the motivations, aims, and content of consecutive versions of AD diagnostic criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We systematically analyzed publications on AD diagnostic criteria between 1984 and 2024.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Early diagnosis and incorporating recent scientific findings are recurring aims for criteria revisions but aims and motivations for revising are often unclear or ambiguous and reflection on previous criteria is lacking. The subsequent criteria, except International Working Group (IWG) 2021/2024, consistently lower the threshold for diagnosing AD and increasingly focus on amyloid β and tau biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Subsequent AD criteria show an increasing “biomarkerization,” but it is often unclear what problems revised criteria should solve and how effective they are. To overcome these limitations, future revisions should evaluate the effectiveness and impacts of previous criteria, and define clear problems and aims.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Early diagnosis and incorporating scientific insights are recurring aims.</li>\u0000 \u0000 <li>The aims of new criteria are often not clearly articulated or ambiguous.</li>\u0000 \u0000 <li>The number of requirements for an AD diagnosis decreases over time.</li>\u0000 \u0000 <li>Consecutive criteria for research and clinical use did not result in clear terminology.</li>\u0000 \u0000 <li>The AD definition is increasingly narrowed to amyloid β and tau.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing visual read tau-PET-negative participants with Alzheimer's disease dementia","authors":"Roos M. Rikken,&nbsp;Emma M. Coomans,&nbsp;Lotte A. de Koning,&nbsp;Denise Visser,&nbsp;Eline Neutelings,&nbsp;Anouk den Braber,&nbsp;Lyduine E. Collij,&nbsp;Sandeep S. V. Golla,&nbsp;for the Alzheimer's Disease Neuroimaging Initiative,&nbsp;Frederik Barkhof,&nbsp;Pieter Jelle Visser,&nbsp;Philip Scheltens,&nbsp;Wiesje M. van der Flier,&nbsp;Ronald Boellaard,&nbsp;Rik Ossenkoppele,&nbsp;Everard G. B. Vijverberg,&nbsp;Elsmarieke van de Giessen,&nbsp;for ADNI","doi":"10.1002/alz.14423","DOIUrl":"https://doi.org/10.1002/alz.14423","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>A subset of amyloid beta (Aβ)-positive Alzheimer's disease (AD) patients is tau-positron emission tomography (PET) negative. We aimed to characterize this subgroup using [¹⁸F]flortaucipir PET visual read (VR), as this is important for prognosis and selection for therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Aβ-positive VR tau-PET-negative AD dementia patients (AD A+T−) were compared to tau-PET-positive AD patients (AD A+T+) and control groups (CU A−T−; CU A+T−) included from the Amsterdam-based cohort and Alzheimer's Disease Neuroimaging Initiative (ADNI). We compared [¹⁸F]flortaucipir binding in an early- and late-stage tau ROI, atrophy, cognition, and co-pathologies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>AD A+T− were older, showed less hippocampal atrophy and slower cognitive decline compared to AD A+T+. In ADNI, AD A+T− showed higher early-stage tau binding compared to both control groups and more late-stage tau compared to CU A−T−, but no tau accumulation over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>VR tau-PET-negative AD patients show neurodegenerative and cognitive processes consistent with the AD trajectory, but milder progression compared to tau-PET-positive AD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We used the novel Food and Drug Administration (FDA)-approved VR method for defining tau-PET positivity.</li>\u0000 \u0000 <li>AD A+T− patients were older and showed less atrophy and cognitive decline than AD A+T+.</li>\u0000 \u0000 <li>We did not find convincing evidence of tau accumulation in AD A+T− or copathologies.</li>\u0000 \u0000 <li>The group of AD A+T− patients is likely very heterogeneous.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14423","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experiences and perceptions of sexism in dementia research careers: A global cross-sectional survey","authors":"Adam Smith,&nbsp;Charlèss Dupont,&nbsp;Diana Karamacoska,&nbsp;Sara Laureen Bartels,&nbsp;Elizabeth A. English,&nbsp;Nathan M. D'Cunha,&nbsp;Darina V. Petrovsky,&nbsp;C. Elizabeth Shaaban","doi":"10.1002/alz.70123","DOIUrl":"https://doi.org/10.1002/alz.70123","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Sexism is prevalent in academia and is a crucial factor driving women out of the academic workforce. However, sexism in dementia research remains underexplored. This study aimed to understand the perceptions and experiences of early-career dementia researchers (ECDRs) with sexism in the field.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>In September/October 2021, a global online survey was conducted targeting ECDRs. The survey assessed their career experiences, including sexism, and was distributed through networks, social media, and e-mail lists. Responses were analyzed using descriptive and inferential statistics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Of the 345 respondents, more than half of the female ECDRs (52%) reported facing sexism in their careers, ranging from overt discrimination to subtle biases. Experiences varied by career stage and location, and many ECDRs reported a lack of institutional support.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings reveal the prevalent nature of sexism in dementia research and highlight the need for targeted interventions to foster a more inclusive research environment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>A global survey revealed 52% of female early-career dementia researchers experience sexism.</li>\u0000 \u0000 <li>Subtle sexism, like microaggressions, impacts confidence, and collaboration choices.</li>\u0000 \u0000 <li>Experiences of sexism vary by geography, with North America reporting higher prevalence.</li>\u0000 \u0000 <li>Assistant professors report higher rates of institutional and overt sexism.</li>\u0000 \u0000 <li>Findings emphasize the need for policies addressing implicit bias and sex inequality.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of Alzheimer's disease genetic factors on limbic white matter microstructure","authors":"Anna Lorenz,&nbsp;Aditi Sathe,&nbsp;Dimitrios Zaras,&nbsp;Yisu Yang,&nbsp;Alaina Durant,&nbsp;Michael E. Kim,&nbsp;Chenyu Gao,&nbsp;Nancy R. Newlin,&nbsp;Karthik Ramadass,&nbsp;Praitayini Kanakaraj,&nbsp;Nazirah Mohd Khairi,&nbsp;Zhiyuan Li,&nbsp;Tianyuan Yao,&nbsp;Yuankai Huo,&nbsp;Logan Dumitrescu,&nbsp;Niranjana Shashikumar,&nbsp;Kimberly R. Pechman,&nbsp;Trevor Bryan Jackson,&nbsp;Abigail W. Workmeister,&nbsp;Shannon L. Risacher,&nbsp;Lori L. Beason-Held,&nbsp;Yang An,&nbsp;Konstantinos Arfanakis,&nbsp;Guray Erus,&nbsp;Christos Davatzikos,&nbsp;Mohamad Habes,&nbsp;Di Wang,&nbsp;Duygu Tosun,&nbsp;Arthur W. Toga,&nbsp;Paul M. Thompson,&nbsp;Elizabeth C. Mormino,&nbsp;Panpan Zhang,&nbsp;Kurt Schilling,&nbsp;Alzheimer's Disease Neuroimaging Initiative (ADNI)The BIOCARD Study TeamThe Alzheimer's Disease Sequencing Project (ADSP),&nbsp;Marilyn Albert,&nbsp;Walter Kukull,&nbsp;Sarah A. Biber,&nbsp;Bennett A. Landman,&nbsp;Sterling C. Johnson,&nbsp;Barbara Bendlin,&nbsp;Julie Schneider,&nbsp;Lisa L. Barnes,&nbsp;David A. Bennett,&nbsp;Angela L. Jefferson,&nbsp;Susan M. Resnick,&nbsp;Andrew J. Saykin,&nbsp;Timothy J. Hohman,&nbsp;Derek B. Archer","doi":"10.1002/alz.70130","DOIUrl":"https://doi.org/10.1002/alz.70130","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>White matter (WM) microstructure is essential for brain function but deteriorates with age and in neurodegenerative conditions such as Alzheimer's disease (AD). Diffusion MRI, enhanced by advanced bi-tensor models accounting for free water (FW), enables in vivo quantification of WM microstructural differences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>To evaluate how AD genetic risk factors affect limbic WM microstructure – crucial for memory and early impacted in disease – we conducted linear regression analyses in a cohort of 2,614 non-Hispanic White aging adults (aged 50.12 to 100.85 years). The study evaluated 36 AD risk variants across 26 genes, the association between AD polygenic scores (PGSs) and WM metrics, and interactions with cognitive status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>AD PGSs, variants in <i>TMEM106B</i>, <i>PTK2B</i>, <i>WNT3</i>, and apolipoprotein E (<i>APOE</i>), and interactions involving <i>MS4A6A</i> were significantly linked to WM microstructure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings implicate AD-related genetic factors related to neurodevelopment (<i>WNT3</i>), lipid metabolism (<i>APOE</i>), and inflammation (<i>TMEM106B</i>, <i>PTK2B, MS4A6A</i>) that contribute to alternations in WM microstructure in older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>AD risk variants in <i>TMEM106B</i>, <i>PTK2B</i>, <i>WNT3</i>, and <i>APOE</i> genes showed distinct associations with limbic FW-corrected WM microstructure metrics.</li>\u0000 \u0000 <li>Interaction effects were observed between <i>MS4A6A</i> variants and cognitive status.</li>\u0000 \u0000 <li>PGS for AD was associated with higher FW content in the limbic system.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APOE and Alzheimer's disease and related dementias risk among 12,221 Hispanics/Latinos","authors":"Sandra Barral,&nbsp;Zikun Yang,&nbsp;Nicole Phillips,&nbsp;Robert C. Barber,&nbsp;Adam M. Brickman,&nbsp;Lawrence S. Honig,&nbsp;Basilio Cieza,&nbsp;Dolly Reyes-Dumeyer,&nbsp;Richard Mayeux,&nbsp;Farid Rajabli,&nbsp;Michael L. Cuccaro,&nbsp;Jeffery M. Vance,&nbsp;Silvia Mejia Arango,&nbsp;Rafael Samper-Ternent,&nbsp;Alejandra Michaels Obregon,&nbsp;Rosa Montesinos,&nbsp;Marcio Soto-Añari,&nbsp;Juan Carlos Duran,&nbsp;Maria Cusicanqui,&nbsp;Ivonne Z. Jimenez Velazquez,&nbsp;Victoria Marca,&nbsp;Maryenela Illanes-Manrique,&nbsp;Mario Cornejo-Olivas,&nbsp;Margaret Pericak-Vance,&nbsp;Rebeca Wong,&nbsp;Sid O'Bryant,&nbsp;Nilton Custodio,&nbsp;Giuseppe Tosto","doi":"10.1002/alz.70138","DOIUrl":"https://doi.org/10.1002/alz.70138","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>Effect of apolipoprotein E (<i>APOE</i>) on Alzheimer's disease and related dementias (ADRD) risk is heterogeneous across populations, with scarce data on Hispanics/Latinos.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p><i>APOE</i> genotype was studied in 12,221 Hispanics/Latinos (per cohort and via metanalysis): Caribbean-Hispanics, Mexicans, Mexican-Americans, and Peruvians/Bolivians. A subsample had longitudinal assessment and plasma p-tau. We tested the modifying effects of global and local ancestries. Results were replicated in an independent Peruvian cohort and brain samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p><i>APOE</i> ε4 effect was strongest in Peruvians/Bolivians (odds ratio [OR] = 6.13, 95% confidence interval [CI] = 2.71–13.83), followed by Mexicans (OR = 4.31, 95% CI = 1.58–11.74), Mexican-Americans (OR = 3.06, 95% CI = 2.04–4.59), and Caribbean-Hispanics (OR = 2.22, 95% CI = 1.99–2.48). Meta-analyses showed OR = 2.32 (95% CI = 2.09–2.57) and OR = 0.81 (95% CI = 0.68–0.97) for the ε4 and ε2 allele, respectively. The <i>APOE</i> ε4 effect was replicated independently in Peruvians (OR = 5.06, 95% CI = 2.48–10.70). ε4 carriers displayed higher ADRD conversions and p-tau levels. Global and local ancestries did not modify ADRD risk, and they were associated with Braak stage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p><i>APOE</i> shows a heterogeneous effect on ADRD risk in our Hispanics/Latinos sample, the largest to date.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The apolipoprotein E (<i>APOE</i>) ε4 effect is stronger in Peruvians/Bolivians than in other Hispanic/Latino groups.</li>\u0000 \u0000 <li>The strong <i>APOE</i> effect size in Peruvians and Bolivians was replicated in a second independent Peruvian cohort.</li>\u0000 \u0000 <li>Meta-analysis for ε4 and ε2 confirmed a significant association with Alzheimer's disease and related dementias (ADRD).</li>\u0000 \u0000 <li>Global and local ancestry do not modify the association between <i>APOE</i> genotype and ADRD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatic and Stem Cell Bank to study the contribution of African ancestry to dementia: African iPSC Initiative","authors":"Mahmoud B. Maina,&nbsp;Murtala B. Isah,&nbsp;Jacob A. Marsh,&nbsp;Zaid Muhammad,&nbsp;Larema Babazau,&nbsp;Abdulrahman Alkhamis Idris,&nbsp;Ekaterina Aladyeva,&nbsp;Nadia Miller,&nbsp;Emma Starr,&nbsp;Katherine J. Miller,&nbsp;Scott Lee,&nbsp;Miguel Minaya,&nbsp;Selina Wray,&nbsp;Oscar Harari,&nbsp;Baba W. Goni,&nbsp;Louise C. Serpell,&nbsp;Celeste M. Karch","doi":"10.1002/alz.70145","DOIUrl":"https://doi.org/10.1002/alz.70145","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Africa, home to 1.4 billion people and the highest genetic diversity globally, harbors unique genetic variants crucial for understanding complex diseases like neurodegenerative disorders. However, African populations remain underrepresented in induced pluripotent stem cell (iPSC) collections, limiting the exploration of population-specific disease mechanisms and therapeutic discoveries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>To address this gap, we established an open-access African Somatic and Stem Cell Bank.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In this initial phase, we generated 10 rigorously characterized iPSC lines from fibroblasts representing five Nigerian ethnic groups and both sexes. These lines underwent extensive profiling for pluripotency, genetic stability, differentiation potential, and Alzheimer's disease and Parkinson's disease risk variants. Clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 technology was used to introduce frontotemporal dementia-associated <i>MAPT</i> mutations (P301L and R406W).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This collection offers a renewable, genetically diverse resource to investigate disease pathogenicity in African populations, facilitating breakthroughs in neurodegenerative research, drug discovery, and regenerative medicine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We established an open-access African Somatic and Stem Cell Bank.</li>\u0000 \u0000 <li>10 induced pluripotent stem cell lines from five Nigerian ethnic groups were rigorously characterized.</li>\u0000 \u0000 <li>Clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 technology was used to introduce frontotemporal dementia-causing <i>MAPT</i> mutations.</li>\u0000 \u0000 <li>The African Somatic and Stem Cell Bank is a renewable, genetically diverse resource for neurodegenerative research.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}