Alzheimer's & Dementia最新文献

{"title":"Differential effects of age and sex on tau pathology propagation in the htau mouse model: A neuropathological and proteomic study","authors":"Andreea-Claudia Kosa,&nbsp;Lidia Lopez-Gutierrez,&nbsp;Kunie Ando,&nbsp;Emilie Doeraene,&nbsp;Emmanuel Aydin,&nbsp;Hinde Lasri,&nbsp;Alain Wathelet-Depauw,&nbsp;Karlien Pieters,&nbsp;David Van Morckhoven,&nbsp;Virginie Imbault,&nbsp;Christine Dubois,&nbsp;Xavier Bisteau,&nbsp;Basile Stamatopoulos,&nbsp;Mariana Igoillo-Esteve,&nbsp;Jean-Pierre Brion,&nbsp;Karelle Leroy","doi":"10.1002/alz.70784","DOIUrl":"10.1002/alz.70784","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Aging is the main risk factor for Alzheimer's disease (AD), acting through still poorly understood mechanisms. AD is associated with the development of a tau pathology, a hallmark lesion propagating in the brain along neuroanatomically connected pathways. This study investigates changes in gene expression and patterns of tau pathology after induction of tau pathology propagation and the effects of age and sex on this propagation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Young and old humanized htau mice were intracerebrally injected with pathological tau from human AD brain to induce tau pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Young and old htau male mice showed similar patterns of tau pathology propagation, whereas the density of tau pathology was increased in young compared to old female mice. Proteomic analysis demonstrated differential expression of proteins involved in endocytosis, autophagosome formation, and tau splicing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The increased tau pathology formation in young female mice suggests that involvement of selected biological mechanisms could occur early in women during their midlife to explain their sensitivity to the development of tau pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Tau pathology induced by human PHF-tau is mainly composed of 3R-tau in htau mice.</li>\u0000 \u0000 <li>Splicing factors favoring 4R-tau are downregulated in mice with tau pathology.</li>\u0000 \u0000 <li>Tau pathology propagation is increased in young females compared to old females.</li>\u0000 \u0000 <li>Proteins implicated in endocytosis and autophagy are modified when tau pathology propagates.</li>\u0000 \u0000 <li>Some protein expressions are similarly modified in young females and during normal aging.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12516240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278844","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 ε4 linked effects on clinical features and neuropathology in dementia with Lewy bodies","authors":"Rong Ye,&nbsp;Anna E. Goodheart,&nbsp;Joseph J. Locascio,&nbsp;Erin C. Peterec,&nbsp;Patrick Stancu,&nbsp;Yanhong Wang,&nbsp;Stephen N. Gomperts","doi":"10.1002/alz.70795","DOIUrl":"10.1002/alz.70795","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Apolipoprotein E (<i>APOE</i>) ε4 is a strong genetic risk factor for Alzheimer's disease (AD) neuropathologic changes, but its contribution to clinical features and pathology in dementia with Lewy bodies (DLB) is less clear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using the National Alzheimer Coordinating Center dataset, we investigated <i>APOE</i> ε4-associated effects on DLB core clinical features and neuropathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In analyses of <i>APOE</i> ε4 carriers, dosage, and genetic risk score, <i>APOE</i> ε4 was associated with lower odds of fluctuating cognition and parkinsonism and higher odds of visual hallucinations. <i>APOE</i> ε4 was associated with greater neocortical Lewy body pathology, partially mediated by AD co-pathology. The severity of fluctuating cognition was associated with Lewy body pathology stage after controlling for AD co-pathology. Visual hallucinations were associated with both Lewy body and AD pathologies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Core clinical features of DLB are sensitive to <i>APOE</i> haplotype. Targeting <i>APOE</i> biology may elucidate DLB pathogenesis and inform therapeutic development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Core clinical features of dementia with Lewy bodies were sensitive to apolipoprotein E (<i>APOE</i>) haplotype.</li>\u0000 \u0000 <li><i>APOE</i> ε4 was associated with a higher likelihood of hallucinations yet a lower likelihood of cognitive fluctuations.</li>\u0000 \u0000 <li><i>APOE</i> ε4 was associated with greater severity of Lewy body pathology, partially mediated by Alzheimer's disease (AD) co-pathology.</li>\u0000 \u0000 <li>Whereas fluctuating cognition was primarily linked to Lewy body pathology, visual hallucinations were associated with both Lewy body and AD neuropathologic changes.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70795","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261562","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":"Neurocognitive disorders, depression, and associated factors in younger and older adults from an urban-marginalized area of Peru","authors":"Monica M. Diaz,&nbsp;Eder Herrera-Perez,&nbsp;Rosa Montesinos,&nbsp;Chhitij Tiwari,&nbsp;Nilton Custodio,&nbsp;Serggio C. Lanata","doi":"10.1002/alz.70798","DOIUrl":"10.1002/alz.70798","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>In urban-marginalized areas of low-to-middle-income countries (LMICs), neurocognitive disorders (NCDs) and depression present significant public health issues, exacerbated by socioeconomic disparities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This study explores the prevalence and risk factors of NCDs and depression among 1064 community-dwelling adults in an urban-marginalized district of Lima, Peru. Structured questionnaires collected demographic, health, and socioeconomic data; neurocognitive assessments and depression screening were conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Mean age was 50.5 years, with 71% female, and a mean of 9.1 years of education. Among older adults, 32% had mild NCD and 4.2% had major NCD; 21.1% of younger adults had any NCD. Nearly 40% of the cohort was depressed. Risk factors for MCI and NCD included lower education, hypertension, and non-Spanish native language, while depression was associated with female sex, lower education, overcrowding, and chronic diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The study emphasizes the need for targeted interventions to address NCDs and mental health in urban-marginalized areas of LMICs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Among older adults, 32% had mild neurocognitive disorder (NCD) and 4.2% had major NCD; 21.1% of younger adults had any NCD.</li>\u0000 \u0000 <li>Nearly 40% of the cohort was depressed.</li>\u0000 \u0000 <li>Risk factors for mild cognitive impairment (MCI) and NCD included lower education, hypertension, and non-Spanish native language, while depression was associated with female sex, lower education, overcrowding, and chronic diseases.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70798","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261563","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":"Apolipoprotein ε4 exacerbates white matter impairment in a mouse model of Aβ amyloidosis by decreasing actively myelinating oligodendrocytes","authors":"Md Mamun Al-Amin,&nbsp;Byungwook Kim,&nbsp;Hande Karahan,&nbsp;Mason D. Tate,&nbsp;Sam P. Walsh,&nbsp;Shweta S. Puntambekar,&nbsp;Stephanie J. Bissel,&nbsp;Bruce T. Lamb,&nbsp;Nian Wang,&nbsp;Jungsu Kim","doi":"10.1002/alz.70791","DOIUrl":"10.1002/alz.70791","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The ε4 allele of the apolipoprotein E (<i>APOE</i>) gene is a risk factor for the development of Alzheimer's disease (AD). <i>APOE4</i> isoform is associated with increased white matter lesions in humans. To identify the underlying mechanisms of white matter impairment associated with <i>APOE4</i>, we investigated the effects of <i>APOE4</i> and <i>APOE3</i> on multiple readouts of the white matter microstructural integrity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using magnetic resonance imaging and immunohistochemistry approaches, we analyzed white matter tracts in 5xFAD mice expressing <i>APOE3</i> (5xFAD;<i>APOE3</i>) or <i>APOE4</i> (5xFAD;<i>APOE4</i>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p><i>APOE4</i> significantly decreased fractional anisotropy, axial diffusivity, and neurite density index, while increasing radial diffusivity and isotropic volume fraction within major white matter tracts. Myelination was reduced in the corpus callosum of 5xFAD;<i>APOE4</i> mice. Mechanistically, <i>APOE4</i> reduced populations of mature and actively myelinating oligodendrocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our results suggest that a decrease in the number of actively myelinating oligodendrocytes may explain myelin loss, leading to white matter impairments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>A robust neurite orientation dispersion and density imaging (NODDI) approach to study the effect of apolipoprotein E (APOE) isoforms on the white matter in 5xFAD mice.</li>\u0000 \u0000 <li>APOE4 reduces neurite density and increases water accumulation in the white matter.</li>\u0000 \u0000 <li>APOE4 disrupts structural connectivity and reduces the betweenness centrality.</li>\u0000 \u0000 <li>APOE4 decreases the number of actively myelinating oligodendrocytes.</li>\u0000 \u0000 <li>A reduction in myelinating oligodendrocyte populations may lead to myelin loss.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261556","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":"Plasma p-tau217 and Aβ42/40 as markers of Aβ pathology in the Lewy body continuum","authors":"Kyung Ah Woo,&nbsp;Eun Jin Yoon,&nbsp;Ryul Kim,&nbsp;Heejung Kim,&nbsp;Seoyeon Kim,&nbsp;Bora Jin,&nbsp;Seungmin Lee,&nbsp;Yu Kyeong Kim,&nbsp;Hyunwoo Nam,&nbsp;Jee-Young Lee","doi":"10.1002/alz.70788","DOIUrl":"10.1002/alz.70788","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study evaluated whether plasma phosphorylated tau-217 (p-tau217), amyloid beta (Aβ)42/40, and their combination could serve as biomarkers of Aβ co-pathology across the Lewy body continuum, where Aβ is frequently observed from prodromal to symptomatic stages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Individuals with dementia with Lewy bodies (DLB), Parkinson's disease (PD), and their shared prodromal stage, isolated rapid eye movement (REM) sleep behavior disorder (iRBD) underwent plasma sampling, Aβ-PET, and cognitive testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Higher plasma p-tau217, lower Aβ42/40, and their interaction were associated with greater Aβ-PET uptake. Individuals with higher-than-median p-tau217 and lower-than-median Aβ42/40 showed the highest Aβ burden. Both biomarkers predicted Aβ-PET positivity, but only p-tau217 correlated with cognition. Among 44 iRBD participants followed prospectively, elevated baseline p-tau217 predicted phenoconversion to overt Lewy body disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Plasma p-tau217 and Aβ42/40 may serve as accessible biomarkers of cerebral Aβ pathology and help identify individuals across the Lewy body continuum who could benefit from Aβ-targeted therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Plasma phosphorylated tau-217 (p-tau217) and amyloid beta (Aβ)42/40 predict cerebral Aβ burden in the Lewy body continuum.</li>\u0000 \u0000 <li>Both biomarkers individually show high accuracy for identifying Aβ positron emission tomography positivity.</li>\u0000 \u0000 <li>Plasma p-tau217, but not Aβ42/40, is associated with cognitive performance.</li>\u0000 \u0000 <li>Elevated plasma p-tau217 predicts future phenoconversion in isolated rapid eye movement sleep behavior disorder.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70788","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261559","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":"Body mass index and blood volume influence plasma biomarkers and positron emission tomography classification in preclinical Alzheimer's disease","authors":"Tovia Jacobs,&nbsp;Courtney O’ Brien,&nbsp;Luisa Figueredo,&nbsp;Alexandra Gogola,&nbsp;Naomi L. Gaggi,&nbsp;Brian Hurwitz,&nbsp;Elizabeth Pirraglia,&nbsp;Shimon Herzog,&nbsp;Jaime Ramos-Cejudo,&nbsp;Timothy M. Shepherd,&nbsp;Priya Palta,&nbsp;Juan Fortea,&nbsp;Thomas M Wisniewski,&nbsp;Rebecca A. Betensky,&nbsp;Brian Lopresti,&nbsp;Michelle M. Mielke,&nbsp;Antonio Convit,&nbsp;Ricardo S. Osorio,&nbsp;for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/alz.70765","DOIUrl":"10.1002/alz.70765","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Blood-based biomarkers (BBMs) are promising tools for Alzheimer's disease (AD) diagnosis, but their accuracy may be affected by body mass index (BMI) and blood volume (BV) through dilution. We investigated how BMI and BV influence BBM concentrations and PET prediction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Data from 241 cognitively unimpaired participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) were examined to evaluate the influence of BMI/BV on BBMs (Aβ_42/40, p-Tau₁₈₁, p-Tau₂₁₇, glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) and BBM-based PET predictions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Elevated BMI/BV associated with lower BBM concentrations, especially for p-Tau₂₁₇ and NfL, independent of brain amyloid burden. BMI-stratified thresholds improved amyloid PET prediction, with higher BBM thresholds and area under the curve (AUC) values seen in normal weight compared to overweight or obese participants. Drastic BMI/BV declines due to weight loss increased BBM variability and systematic PET misclassification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Adjusting for BMI/BV in BBM-based diagnostics appears to improve accuracy and reliable detection of AD pathology, especially in preclinical stages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Body mass index (BMI) and blood volume (BV) significantly influenced plasma BBM concentrations in cognitively unimpaired (CU) individuals.</li>\u0000 \u0000 <li>Blood-based biomarkers (BBMs) associated more strongly with BV than with BMI.</li>\u0000 \u0000 <li>Dilution effects were independent of brain amyloid burden.</li>\u0000 \u0000 <li>BMI-stratified BBM thresholds improved amyloid positron emission tomography (PET) classification accuracy.</li>\u0000 \u0000 <li>Declines in BMI/BV resulted in PET prediction bias and systematic errors.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12514939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273366","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":"Development and evaluation of image preprocessing pipelines for the Centiloid method on Down Syndrome data","authors":"Weiquan Luo,&nbsp;Davneet S Minhas,&nbsp;Ethan D Rubenstein,&nbsp;David N Situ,&nbsp;Sarah K Royse,&nbsp;Beau M Ances,&nbsp;Bradley T Christian,&nbsp;Ann D Cohen,&nbsp;Benjamin L Handen,&nbsp;William E Klunk,&nbsp;Dana L Tudorascu,&nbsp;Shahid Zaman,&nbsp;Charles M Laymon,&nbsp;Alzheimer's Biomarkers Consortium–Down Syndrome (ABC-DS) Investigators","doi":"10.1002/alz.70712","DOIUrl":"10.1002/alz.70712","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>Centiloid provides a standardized process to quantify brain amyloid in which a subject's T1 magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans are registered and warped to Montreal Neurological Institute 152 space using prescribed procedures. The method has a high failure rate in Down syndrome (DS) subjects from the Neurodegeneration in Aging Down Syndrome (NiAD) project. We evaluate imaging preprocessing methods (PMs) to improve the DS success rate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>PMs were constructed from combinations of image origin reset, filtering, MRI bias correction, and MRI skull stripping. Centiloid results were evaluated for adherence to standards using The Global Alzheimer's Association Interactive Network dataset. PMs were also evaluated using the NiAD dataset to judge their suitability for the DS population. DS PM evaluation procedures were developed corresponding to those specified for non-DS populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Five accepted PMs improved the Centiloid-processing success rate in the DS cohort from 61.3% to 95.6%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The identified combinations of preprocessing steps substantially improved the success rate of Centiloid processing in DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Image preprocessing pipeline is proposed for Centiloid analysis of DS.</li>\u0000 \u0000 <li>Preprocessing pipelines are evaluated for adherence to Centiloid standards.</li>\u0000 \u0000 <li>Pipelines are evaluated for improvement in yield of usable imaging data.</li>\u0000 \u0000 <li>Preprocessing of amyloid imaging data resulted in a large yield improvement.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70712","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261558","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":"Lecanemab treatment for Alzheimer's Disease of varying severities and associated plasma biomarkers monitoring: A multi-center real-world study in China","authors":"Sihui Chen,&nbsp;Ruwei Ou,&nbsp;Qianqian Wei,&nbsp;Chunyu Li,&nbsp;Wei Song,&nbsp;Bi Zhao,&nbsp;Jing Yang,&nbsp;Jiajia Fu,&nbsp;Yuanzheng Ma,&nbsp;Jiyong Liu,&nbsp;Xiangming Wang,&nbsp;Dengfu Fang,&nbsp;Tao Hu,&nbsp;Li Xiao,&nbsp;Shushan Zhang,&nbsp;Rui Huang,&nbsp;Xiaoyan Guo,&nbsp;Fei Feng,&nbsp;Xueping Chen,&nbsp;Huifang Shang","doi":"10.1002/alz.70750","DOIUrl":"10.1002/alz.70750","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We investigated real-world efficacy, safety, and plasma biomarker dynamics of Lecanemab in Chinese patients with Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A multi-center prospective cohort study enrolled 68 AD patients. Cognitive scales and plasma biomarkers were assessed at baseline (V0), 2.5 months (V1), and 7 months (V2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Alzheimer's Disease Assessment Scale-Cognitive Subscale 14-item version (ADAS-cog14) scores improved significantly at both follow-ups, and plasma p-tau181 consistently declined. Both p-tau181 and p-tau217 correlated with cognition and partially predicted treatment response (area under the curve [AUC] = 0.734 and 0.713). Mixed-effects modeling confirmed their dynamic association with ADAS-cog14 scores. Subgroup analyses indicated benefits across sex and <i>apolipoprotein E4</i> status, while moderate-to-severe cases showed limited response. Lecanemab was well tolerated, with asymptomatic amyloid-related imaging abnormalities in 17.65% and mild infusion reactions in 5.88%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings support the short-term efficacy and safety of Lecanemab in early AD and highlight plasma biomarkers as a treatment-responsive biomarker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Lecanemab improved cognitive function in Chinese patients with mild cognitive impairment due to Alzheimer's disease (AD-MCI) and mild AD over a short period.</li>\u0000 \u0000 <li>Plasma p-tau181 and p-tau217 showed significant correlation with cognitive scores, and their baseline level could partially predict the efficacy of lecanemab.</li>\u0000 \u0000 <li>Lecanemab showed a favorable safety profile with low, manageable rates of amyloid-related imaging abnormalities (ARIA) and infusion reactions.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70750","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255335","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":"Retinal microvascular alterations in Alzheimer's disease: Linking blood plasma biomarkers and cerebral small vessel pathology","authors":"William Robert Kwapong,&nbsp;Ning Wu,&nbsp;Weihong Lin,&nbsp;Jianing Shen,&nbsp;Youjie Wang,&nbsp;Jiajing Qian,&nbsp;Caiyun Wen,&nbsp;Xiaoqian Luan,&nbsp;Yuntao Liu,&nbsp;Haoran Cheng,&nbsp;Huihua Qiu,&nbsp;Carol Y. Cheung,&nbsp;Chunwen Zheng,&nbsp;Yinhe Liu,&nbsp;Yunjun Yang,&nbsp;Vincent Mok,&nbsp;Zhen Wang","doi":"10.1002/alz.70745","DOIUrl":"10.1002/alz.70745","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>Retinal microvascular alterations, detectable via color fundus photography (CFP), may reflect cerebral microvascular pathology in Alzheimer's disease (AD). However, their associations with blood-based biomarkers and cerebral small vessel disease (SVD) remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This cross-sectional study included 72 AD patients and 82 cognitively unimpaired (CU) controls. Participants underwent CFP, plasma biomarker analysis (amyloid beta [Aβ]42, Aβ42/40, phosphorylated tau [p-tau]181, p-tau217), and 3T magnetic resonance imaging. Retinal microvascular metrics (vessel density [VD], fractal dimension [FD]) were analyzed alongside SVD markers (white matter hyperintensities [WMHs], SVD burden) and medial temporal lobe atrophy (MTA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>AD patients exhibited significantly reduced VD and FD compared to CU (all <i>p</i> &lt; 0.001), with strong diagnostic accuracy (area under the curve: 0.969 for VD; 0.904 for FD). Retinal microvascular impairment correlated with plasma biomarkers (lower Aβ42, Aβ42/40; elevated p-tau181, p-tau217; all <i>p</i> &lt; 0.05) and neuroimaging markers of SVD (WMHs, MTA; all <i>p</i> &lt; 0.05). Apolipoprotein E ε4 carriers showed more severe retinal microvascular damage (<i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Retinal microvascular alterations, assayed via CFP, are linked to AD-specific proteinopathy and cerebrovascular pathology, supporting CFP as a scalable, non-invasive tool for AD biomarker discovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Retinal microvasculature assayed via color fundus photography (CFP) is sensitive to microvascular damage and can differentiate Alzheimer's disease (AD) from cognitively unimpaired controls.</li>\u0000 \u0000 <li>Retinal microvascular damage in AD is associated with phosphorylated tau [p-tau]181, p-tau217, p-tau217/amyloid beta (Aβ)42, and increased amyloid burden (lower Aβ42 and Aβ42/40).</li>\u0000 \u0000 <li>Retinal microvascular damage in AD is associated with increased cerebral small vessel burden.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70745","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246938","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":"Validation of a MIND diet screener in older adults","authors":"Desarae A. Dempsey,&nbsp;Puja Agarwal,&nbsp;Shane Fernandez,&nbsp;Jared R. Brosch,&nbsp;Sujuan Gao,&nbsp;Daniel O. Clark,&nbsp;Frederick W. Unverzagt,&nbsp;Liana G. Apostolova,&nbsp;David G. Clark,&nbsp;Martin R. Farlow,&nbsp;Sunu Mathew,&nbsp;Sophia Wang,&nbsp;Michelle Quirke,&nbsp;Yolanda Graham-Dotson,&nbsp;Colette Blach,&nbsp;Leyla Schimmel,&nbsp;Rima Kaddurah-Daouk,&nbsp;Andrew J. Saykin,&nbsp;Shannon L. Risacher,&nbsp;Alzheimer Gut Microbiome Project Consortium","doi":"10.1002/alz.70766","DOIUrl":"10.1002/alz.70766","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Higher adherence to the Mediterranean-DASH (Dietary Approaches to Stop Hypertension) Intervention for Neurodegenerative Delay (MIND) diet has been associated with reduced Alzheimer's disease (AD) risk. This study assessed the validity of a brief 15-item MIND diet screener compared to a comprehensive food frequency questionnaire (FFQ).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The validity of an adapted MIND diet screener relative to the VioScreen FFQ was evaluated in 92 older adults from the Indiana Alzheimer's Disease Research Center (IADRC). Correlation coefficients and tertile-based classification statistics were used, and FFQ nutrient profiles were examined across screener-based MIND diet tertiles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>MIND diet scores from the screener showed strong positive correlation (<i>r</i> = 0.71, <i>ρ</i> = 0.70, <i>p</i> &lt; 0.001) and comparable ranking ability (63% correctly classified, 1% grossly misclassified, k_w= 0.67) compared to those from the FFQ, as well as significant associations with nutrient profiles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>The MIND diet screener is an acceptable, time-efficient tool for estimating MIND diet scores in older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The MIND diet screener effectively differentiated participants by diet quality.</li>\u0000 \u0000 <li>Agreement between instrument scores was consistent across diagnostic groups.</li>\u0000 \u0000 <li>Reliability of the screener over approximately 1 year was comparable to the FFQ.</li>\u0000 \u0000 <li>The MIND diet screener is an acceptable tool for use in time-constrained settings.</li>\u0000 \u0000 <li>Future studies should confirm validity using objective biomarkers.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70766","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247016","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}