Alzheimer's & Dementia最新文献

{"title":"Correction to \"Participant perspectives on online interventions for diverse caregivers of persons living with dementia\"","authors":"","doi":"10.1002/alz.70736","DOIUrl":"10.1002/alz.70736","url":null,"abstract":"<p>C. Barrio, J. Liang, Y. I. Cordero, M. P. Aranda, <i>Alzheimers Dement</i>.2025 Jun;21(6):e70324. doi: 10.1002/alz.70324.</p><p>We apologize for this error.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70736","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116420","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":"Demographically adjusted normative data among Peruvians with diverse education levels for version 3 of the Alzheimer's Disease Centers’ neuropsychological test battery in the Uniform Data Set","authors":"Gregory Brown,&nbsp;Diego Bustamante-Paytan,&nbsp;María Fe Albujar Pereira,&nbsp;Jose Huilca,&nbsp;Belén Custodio,&nbsp;Katherine Agüero,&nbsp;Graciet Verastegui,&nbsp;Zadith Yauri,&nbsp;Pamela Bartolo,&nbsp;Daniela Bendezu,&nbsp;Rosa Montesinos,&nbsp;Nilton Custodio","doi":"10.1002/alz.70671","DOIUrl":"10.1002/alz.70671","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Demographically adjusted norms are essential for interpreting cognitive tests, yet none exist in Peru for the Alzheimer's Disease Centers’ (ADCs) neuropsychological test battery, especially among low-education populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We assessed 340 healthy adults (ages 43–79, 70% female), balanced by education level (0–6 years, <i>n</i> = 173; ≥ 7 years, <i>n</i> = 167). Participants completed the Uniform Data Set version 3 Neuropsychological Battery (UDS3-NB). Normative values were generated using linear regression with age, education, and sex as predictors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Education groups were matched for age (<i>p</i> = 0.970) and sex (<i>p</i> = 0.904). Neuropsychological measurements varied significantly between education groups, with education emerging as the primary influential factor across all measures, except semantic fluency: vegetables.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study provides comprehensive normative cognitive data for Peruvian adults across a range of education levels, which will assist in the more precise identification of cognitive impairments. Clinicians can determine individual <i>z</i> scores for each neuropsychological measure with the included calculator.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We developed demographically adjusted normative data and a <i>z</i> score calculator for the Uniform Data Set version 3 Neuropsychological Battery among Peruvian adults.</li>\u0000 \u0000 <li>Recruitment was balanced by education level (0–6 vs. ≥ 7 years) to reflect the diverse educational backgrounds in Peru.</li>\u0000 \u0000 <li>Education was the strongest predictor of performance across most cognitive tests, particularly for working memory/executive tasks.</li>\u0000 \u0000 <li>These normative data support more accurate cognitive assessments and dementia diagnoses in Peruvian populations.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70671","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127322","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":"Imaging microtubule dynamics: A new frontier in biomarker development for neurodegenerative diseases","authors":"Naresh Damuka,&nbsp;Samuel N. Lockhart,&nbsp;Kiran K. Solingapuram Sai","doi":"10.1002/alz.70670","DOIUrl":"10.1002/alz.70670","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Microtubules (MTs) are essential components of the neuronal cytoskeleton, playing key roles in intracellular transport, synaptic function, and overall neuronal integrity. Although MT dynamics and MT-binding agents have been studied extensively, their potential as biomarkers in neurodegenerative diseases has received limited attention. Emerging evidence suggests that MT destabilization is one of the earliest pathological events in Alzheimer's disease, Parkinson's disease, and other related disorders. This review highlights MT dysregulation as a promising marker of early neurodegenerative changes and discusses recent advances in imaging tools, particularly positron emission tomography (PET), that enable in vivo visualization of MT dynamics. We focus on the development and application of novel MT-targeting PET radiotracers, such as [¹¹C]MPC-6827, which demonstrate high specificity for destabilized MTs and excellent brain uptake. To our knowledge, this is the first comprehensive review emphasizing MT alterations as a translational imaging biomarker, offering a new perspective in the early detection and monitoring of neurodegenerative diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Microtubule (MT) instability is an early and underrecognized event in neurodegenerative disease pathogenesis and may precede classical hallmarks of Alzheimer's disease pathology.</li>\u0000 \u0000 <li>MT dysregulation holds promise as a novel diagnostic biomarker, offering new opportunities for early detection and disease monitoring in Alzheimer's disease, Parkinson's disease, and related disorders.</li>\u0000 \u0000 <li>Recent advances in MT-targeted positron emission tomography imaging, particularly with [¹¹C]MPC-6827, enable non-invasive, in vivo visualization of MT dynamics with high specificity and brain penetration.</li>\u0000 \u0000 <li>Cross-species validation of MT imaging, from rodent models to non-human primates and humans, demonstrates strong translational potential, supporting its future clinical application.</li>\u0000 \u0000 <li>Integration of MT imaging with established amyloid, tau, and neuroinflammation markers enhances diagnostic precision, supports early intervention strategies, and enables more personalized approaches to neurodegenerative disease care.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70670","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116421","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 relationship of soluble tau species with Alzheimer's disease amyloid plaque removal and tau pathology","authors":"Eric M. McDade,&nbsp;Nicolas R. Barthélemy,&nbsp;Guoqiao Wang,&nbsp;Yan Li,&nbsp;Yuchen Cao,&nbsp;Brian Gordon,&nbsp;Tammie L. S. Benzinger,&nbsp;David Clifford,&nbsp;Alison M. Goate,&nbsp;Alan E. Renton,&nbsp;Jason Hassenstab,&nbsp;Jorge J. Llibre-Guerra,&nbsp;Richard J. Perrin,&nbsp;Chengjie Xiong,&nbsp;Carlos Cruchaga,&nbsp;Catherine J. Mummery,&nbsp;Sarah B. Berman,&nbsp;James Lah,&nbsp;Erik D. Roberson,&nbsp;Christopher Van Dyck,&nbsp;Serge Gauthier,&nbsp;Colin L. Masters,&nbsp;Mario Masellis,&nbsp;Tobias Bittner,&nbsp;Roy Yaari,&nbsp;Jasmeer Chhatwal,&nbsp;Patricio Chrem,&nbsp;William Brooks,&nbsp;Kazushi Suzuki,&nbsp;Johannes J. Levin,&nbsp;Mathias Jucker,&nbsp;John Ringman,&nbsp;David Wallon,&nbsp;Takeshi Ikeuchi,&nbsp;Jae-Hong Lee,&nbsp;Jee Hoon Roh,&nbsp;Peter Schofield,&nbsp;Nick C. Fox,&nbsp;Natalie S. Ryan,&nbsp;Jonathan Vöglein,&nbsp;Celeste Karch,&nbsp;Laura Ibáñez,&nbsp;Gregory S. Day,&nbsp;Raquel Sánchez-Valle,&nbsp;Alisha Daniels,&nbsp;John C. Morris,&nbsp;Charlene Supnet-Bell,&nbsp;Allan I. Levey,&nbsp;Randall J. Bateman,&nbsp;The DIAN-TU Study Team and DIAN Obs Team","doi":"10.1002/alz.70689","DOIUrl":"10.1002/alz.70689","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>Tau-derived cerebrospinal fluid (CSF) biomarkers correlate with amyloid-beta (Aβ) plaques or tau tangles in Alzheimer's disease (AD). This study assessed the effects of long-term anti-Aβ antibodies on amyloid plaques, tau tangles, and CSF tau species to determine the relationships between them.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A post-hoc analysis of the DIAN-TU-001 trial (NCT01760005) examined 142 participants at risk for dominantly inherited AD randomized to solanezumab (<i>n</i> = 50), gantenerumab (<i>n</i> = 52), or placebo (<i>n</i> = 40). High-resolution mass spectrometry quantified CSF tau species over four years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Phosphorylated tau (p-tau) species (153, 181, 217, 231) increased early in preclinical AD but were reduced with gantenerumab-mediated Aβ plaque reduction. Nearly a decade later, MTBR-tau243 and p-tau205 increased, showing no association with Aβ reduction, aligning with tau tangle pathology progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Initially changing soluble p-tau species track Aβ plaque reduction, while ptau205 and MTBR-243 reflect tau tangle pathology, informing different pathways of therapeutic strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>p-tau217 and p-tau231 correlate with Aβ-PET and respond to Aβ-plaque lowering therapies.</li>\u0000 \u0000 <li>Aβ immunotherapy trials support a direct link between p-tau changes and Aβ plaques</li>\u0000 \u0000 <li>Gantenerumab reduces Aβ plaques but does not affect tau NFT-related biomarkers.</li>\u0000 \u0000 <li>Blood-based p-tau217 assays may provide a non-invasive tool to monitor Aβ therapies.</li>\u0000 \u0000 <li>MTBR-tau243 strongly correlates with tau PET and tracks NFT pathology progression.</li>\u0000 \u0000 <li>Further studies are needed to validate tau biomarkers for tracking NFT-targeting therapies.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70689","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117188","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":"Correction to \"Sex differences in the clinical manifestation of autosomal dominant frontotemporal dementia\"","authors":"","doi":"10.1002/alz.70757","DOIUrl":"10.1002/alz.70757","url":null,"abstract":"<p>Memel M, Staffaroni AM, Ilan-Gala I, et al. Sex differences in the clinical manifestation of autosomal dominant frontotemporal dementia. <i>Alzheimers Dement</i>. 2025;21(4):e14630. https://doi.org/10.1002/alz.14630</p><p>The name of the third author is incorrect. “Ilan-Gala I” should be replaced by Illan-Gala I.</p><p>We apologize for this error.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70757","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116415","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":"One-carbon metabolism modulates miR-29a–DNA methylation crosstalk in Alzheimer's disease","authors":"Tiziana Raia,&nbsp;Rosaria A. Cavallaro,&nbsp;Luiza Diniz Ferreira Borges,&nbsp;Stefano Cinti,&nbsp;Mariano Bizzarri,&nbsp;Isidre Ferrer,&nbsp;Marco Lucarelli,&nbsp;Andrea Fuso","doi":"10.1002/alz.70703","DOIUrl":"10.1002/alz.70703","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease (AD)’s multifactorial nature stresses the role of epigenetics in affecting different pathological pathways. We demonstrated that one-carbon metabolism epigenetically impacts AD-like phenotype. Here, we investigated the crosstalk between methylation and microRNAs in AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We altered one-carbon metabolism to induce hypo- and hyper-methylation, in SK-N-BE neuroblastoma cells and TgCRND8 mice. miRNAs were profiled through a polymerase chain reaction array, then we focused on <i>miR-29a</i> expression and methylation of its genomic locus. Finally, we assessed <i>miR-29a</i> expression and methylation in the brain of AD subjects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p><i>MiR-29a</i> was repressed in hypomethylating and expressed in hypermethylating conditions. The expression of <i>miR-29a</i> and of its target, <i>BACE1</i>, was inversely correlated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>We demonstrated for the first time that <i>miR-29a</i> is modulated by one-carbon metabolism through DNA methylation, disclosing the molecular mechanisms regulating <i>BACE1</i> expression in AD. These data confirm <i>miR-29a</i>’s protective role in AD and support <i>miR-29a</i> as a potential biomarker for AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70703","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127320","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":"Expanding the horizon of sex-specific proteomic insights in Alzheimer's disease","authors":"Yue Zhou,&nbsp;Shuang Liu,&nbsp;Lizhi Chen","doi":"10.1002/alz.70725","DOIUrl":"10.1002/alz.70725","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;The recent study by Mei et al. provides a pivotal contribution to understanding sex differences in Alzheimer's disease (AD) through comprehensive proteomic profiling of the dorsolateral prefrontal cortex (DLPFC).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; By identifying 10 proteins with sex-specific interactions in AD pathogenesis, cognitive trajectories, and cerebral pathologies, this work advances the field beyond transcriptomic analyses and highlights the importance of sex-aware biomarker discovery. We commend the authors for their rigorous approach and propose additional perspectives to further contextualize these findings within the broader landscape of AD research.&lt;/p&gt;&lt;p&gt;First, the identification of sex-biased proteins linked to estrogen signaling (e.g., PLCD3, SLC22A5) aligns with emerging evidence that estrogen receptor activity modulates synaptic plasticity and neuroinflammation in a sex-dependent manner.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; For instance, G protein-coupled estrogen receptor (GPER) activation enhances phospholipase C signaling, potentially influencing amyloid beta clearance.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; These findings resonate with epidemiological studies showing that estrogen depletion in postmenopausal women accelerates AD-related cognitive decline.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Further investigation into how estrogen-responsive proteins interact with apolipoprotein E genotype, a known modifier of AD risk, could clarify why females exhibit greater resilience to early amyloid deposition despite higher lifetime AD incidence.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Second, the association of S100A12 (a pro-inflammatory mediator) and MTFR1L (a mitochondrial fusion regulator) with sex-specific cognitive decline underscores the interplay between neuroinflammation and bioenergetic dysfunction in AD. Elevated S100A12 colocalizes with amyloid plaques and correlates with microglial activation in AD brains,&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; and neuroinflammatory responses are more pronounced in females with AD neuropathology.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; Meanwhile, mitochondrial dynamics are critical for maintaining neuronal connectivity, and sex differences in mitochondrial gene expression have been reported in aging brains.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; Integrating these proteomic results with metabolomic or single-cell transcriptomic datasets may reveal how inflammatory and metabolic pathways converge to drive sex-divergent disease trajectories.&lt;/p&gt;&lt;p&gt;Third, the study's focus on the DLPFC, a region affected relatively late in AD, raises intriguing questions about whether sex-specific proteomic signatures emerge earlier in vulnerable regions like the entorhinal cortex or hippocampus. Prior work has shown that tau propagation follows distinct spatial patterns in males and females, with females exhibiting faster neocortical spread independent of amyloid burden.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; Validating the 10 candidate proteins in preclinical cohorts or fluid biomarkers (e.g., ce","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111354","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":"Comparison of amyloid PET acquired through standardized and unstandardized protocols","authors":"Karly A. Cody,&nbsp;Andrzej Sokolowski,&nbsp;Lucah Medina Guerra,&nbsp;Philip S. Insel,&nbsp;William J. Jagust,&nbsp;Theresa M. Harrison,&nbsp;Elizabeth C. Mormino","doi":"10.1002/alz.70697","DOIUrl":"10.1002/alz.70697","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Amyloid positron emission tomography (PET) scans collected by Alzheimer's Disease Research Centers (ADRCs) include site-specific “mixed protocols” and, since 2021, standardized protocols through the Standardized, Centralized AD/ADRD Neuroimaging initiative. We compared amyloid PET from cohorts using unstandardized versus standardized pre-processing protocols.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Across cohorts, amyloid measured in Centiloids (CLs) was derived from 18F-florbetapir (FBP), 18F-florbetaben (FBB), 11C-Pittsburgh compound B (PIB), and 18F-NAV4694 (NAV) scans using identical magnetic resonance imaging–free post-processing pipelines. We evaluated CL distributions across cohorts and tracers using Gaussian mixture models (GMMs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Within each tracer, GMM-derived amyloid negative (A–) CL distributions were similar across cohorts. PIB and NAV showed lower CL variability in the A– range than FBP and FBB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Consistent post-processing yielded comparable A– distributions within tracer across cohorts with heterogeneous pre-processing protocols, supporting future ADRC PET data integration. Reduced variability in A– classes for PIB and NAV suggest that lower positivity thresholds may be appropriate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Alzheimer's Disease Research Center (ADRC) amyloid positron emission tomography (PET) includes unstandardized and standardized pre-processing.</li>\u0000 \u0000 <li>With consistent post-processing, amyloid-negative (A–) Centiloids (CLs) were similar despite variable pre-processing.</li>\u0000 \u0000 <li>CLs from 11C-Pittsburgh compound B and 18F-NAV4694 were less variable than 18F-florbetaben and 18F-florbetapir.</li>\u0000 \u0000 <li>Similar A– CLs across variable pre-processing supports combining ADRC amyloid PET.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70697","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111361","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":"Shifting care patterns: How Medicaid policies shape family and formal care use","authors":"Johanna Thunell,&nbsp;Elise M. Parrish,&nbsp;Katherine E. M. Miller","doi":"10.1002/alz.70715","DOIUrl":"10.1002/alz.70715","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Medicaid programs can support aging in place by paying for care provided by direct care workers (i.e., formal care) and providing financial support, education, and training to otherwise unpaid family members and friends (i.e., family care).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We used nationally representative data of adults 70 years and older with functional limitation(s)—and the subsamples with dementia, enrolled in Medicaid, or rural residents—and multinomial regressions to estimate the relationship between Medicaid waivers paying family caregivers and the types of care received.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Adjusting for demographics and family structure, living in a state with waiver payments for family caregivers decreased the probability of receiving formal care alone and increased the probability of receiving family care among persons living with dementia, Medicaid beneficiaries, and rural residents.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Understanding how policies incentivize caregiving has implications for broader discussions to (1) address workforce supply concerns and (2) mitigate economic consequences of family caregiving.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Medicaid Home and Community-Based Services (HCBS) play a critical role in addressing the care needs of community-dwelling older adults.</li>\u0000 \u0000 <li>Medicaid programs paying family members for care reduced use of formal care.</li>\u0000 \u0000 <li>The relationship was strongest among persons with dementia, Medicaid, and rural residents.</li>\u0000 \u0000 <li>These findings have implications for workforce shortages and supports for caregivers.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70715","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111414","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":"Response to the letter titled “Expanding the Horizon of Sex-Specific Proteomic Insights in Alzheimer's Disease”","authors":"Zhen Mei,&nbsp;Aliza P. Wingo,&nbsp;Thomas S. Wingo","doi":"10.1002/alz.70724","DOIUrl":"10.1002/alz.70724","url":null,"abstract":"<p>Dear Editor,</p><p>We thank Zhou et al. for their interest in our recent work and for providing additional context around our findings. As they suggested, we examined the intersectional effect of apolipoprotein E (<i>APOE)</i> ε4 status by adding a three-way interaction term (sex × trait × <i>APOE</i> ε4) into our models. This allowed us to test whether the sex × trait interactions differed by <i>APOE</i> ε4 status. As shown in Table 1, we continue to see significant sex × trait interactions without significant three-way interactions. These results suggest that the sex-biased disease associations are independent of <i>APOE</i> ε4 dosage, but we acknowledge that at our current sample size is likely underpowered to detect higher ordered interactions.</p><p>We agree with Zhou et al. that integrating our findings with single cell transcriptomics datasets is an important next step, given the evidence of sex-biased gene expression in specific cell types such as microglia.<span>¹</span> Future studies could also investigate whether genetic or epigenic mechanisms may contribute to the observed sex-biased disease associations. This hypothesis is supported by our prior work which has identified 150 proteins with sex-biased protein quantitative trait loci (pQTLs) in human brain proteomes.<span>²</span> Moreover, sex hormones have been shown to regulate chromatin states in males and female neurons,<span>³</span> and microRNAs were also identified as sex-specific regulators in the microglial transcriptome and tau pathology.<span>⁴</span> Studying the potential genetic and epigenetic regulation of these sex-biased proteins and their interactions with sex hormones will advance our understanding of sex difference in Alzheimer's disease (AD).</p><p>We agree that it is also important to examine other brain regions that might be affected in the early stages of AD and to expand omics analysis across diverse populations. The limited availability of <i>post mortem</i> brain tissue presents significant challenges for conducting large-scale studies and examining sex-based or other higher-ordered interactions. Using less invasive biospecimens, such as plasma and cerebrospinal fluid (CSF), to test these sex-specific brain proteins as fluid biomarkers in AD will be an important direction for future research.</p><p>Sincerely,</p><p>Zhen Mei, Aliza P. Wingo, Thomas S. Wingo</p><p>The authors declare no competing interests. Author disclosures are available in the supporting information</p><p>This work was supported by I01 BX003853 (A.P.W.); IK4 BX005219 (A.P.W.); I01 BX005686 (A.P.W.); R01 AG075827 (A.P.W., T.S.W.); R01 AG072120 (A.P.W., T.S.W.); R01 AG079170 (T.S.W.); U01 AG088425 (T.S.W.). ROS/MAP is supported by P30AG10161, P30AG72975, R01AG15819, R01AG17917, U01AG46152, and U01AG61356.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111358","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}