Alzheimer's & Dementia最新文献

{"title":"Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research","authors":"Karen Nuytemans, Sanne Franzen, Iris J. Broce, Paulo Caramelli, Ratnavalli Ellajosyula, Elizabeth Finger, Veer Gupta, Vivek Gupta, Ignacio Illán-Gala, Samantha M. Loi, Darby Morhardt, Yolande Pijnenburg, Katya Rascovsky, Monique M. Williams, Jennifer S. Yokoyama, Juliana Acosta-Uribe, Rufus Akinyemi, Suvarna Alladi, Biniyam A. Ayele, Yavuz Ayhan, Renelle Bourdage, Sheila Castro-Suarez, Leonardo Cruz de Souza, Penny Dacks, Sterre C. M. de Boer, Jessica de Leon, Shana Dodge, Stephanie Grasso, Nupur Ghoshal, Vidyulata Kamath, Fiona Kumfor, Jordi A. Matias-Guiu, Pauline Narme, T. Rune Nielsen, Daniel Okhuevbie, Stefanie Piña-Escudero, Ramiro Ruiz-Garcia, Brigid Ryan, Marta Scarioni, Andrea Slachevsky, Aida Suarez-Gonzalez, Boon Lead Tee, Elena Tsoy, Hulya Ulugut, Chiadi U. Onyike, Ganesh M. Babulal","doi":"10.1002/alz.14312","DOIUrl":"https://doi.org/10.1002/alz.14312","url":null,"abstract":"Frontotemporal dementia (FTD) is one of the leading causes of young-onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure. This perspective paper was produced by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) and discusses the field's current status on the cross-cultural aspects of basic and translational research in FTD (including that focused on epidemiology, genetics, biomarkers, and treatment). It subsequently provides a summary of gaps and needs to address the disparities and advance global FTD biomedical research.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"41 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The ADNI Administrative Core: Ensuring ADNI's success and informing future AD clinical trials","authors":"Rachel L. Nosheny, Melanie Miller, Catherine Conti, Derek Flenniken, Miriam Ashford, Adam Diaz, Juliet Fockler, Diana Truran, Winnie Kwang, Shaveta Kanoria, Dallas Veitch, Robert C. Green, Michael W. Weiner","doi":"10.1002/alz.14311","DOIUrl":"https://doi.org/10.1002/alz.14311","url":null,"abstract":"The Alzheimer's Disease Neuroimaging Initiative (ADNI) Administrative Core oversees and coordinates all ADNI activities, to ensure the success and maximize the impact of ADNI in advancing Alzheimer's disease (AD) research and clinical trials. It manages finances and develops policies for data sharing, publications using ADNI data, and access to ADNI biospecimens. The Core develops and executes pilot projects to guide future ADNI activities and identifies key innovative methods for inclusion in ADNI. For ADNI4, the Administrative Core collaborates with the Engagement, Clinical, and Biomarker Cores to develop and evaluate novel, digital methods and infrastructure for participant recruitment, screening, and assessment of participants. The goal of these efforts is to enroll 500 participants, including > 50% from underrepresented populations, 40% with mild cognitive impairment, and 80% with elevated AD biomarkers. This new approach also provides a unique opportunity to validate novel methods.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"11 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood biomarkers in Down syndrome: Facilitating Alzheimer's disease detection and monitoring","authors":"Melissa E. Petersen, Lisi Flores-Aguilar, Elizabeth Head, Laia Montoliu-Gaya, Andre Strydom, Sarah E. Pape, Juan Fortea, Nicholas J. Ashton, Chinedu Udeh-Momoh, Sid E. O'Bryant, Dwight German, Florin Despa, Mark Mapstone, Henrik Zetterberg","doi":"10.1002/alz.14364","DOIUrl":"https://doi.org/10.1002/alz.14364","url":null,"abstract":"Blood-based biomarkers continue to be explored for disease detection, monitoring of progression, and therapeutic outcomes as the diagnostic determination of Alzheimer's Disease in Down Syndrome (DS-AD) remains challenging in clinical settings. This perspective highlights the current status of this effort. Overall, amyloid (A), tau (T), and neurodegeneration (AT[N]) blood-based biomarkers have been shown to increase with disease pathology for individuals with DS. Phosphorylated tau biomarkers (p-tau217, p-tau181) have been consistently shown to track disease progression for DS-AD and are likely good candidates for use in clinical settings. Biomarkers of inflammation (glial fibrillary acidic protein) also show promise; however, additional work is needed. Findings from stability work of blood-based biomarkers conducted among non-DS also support the potential longitudinal utility of biomarkers such as neurofilament light chain and p-tau181 in DS. Gaps in our knowledge are highlighted, and a potential role for sex differences in biomarker outcomes is noted, along with recommendations for determining the appropriate context of use when translating biomarkers into clinical applications.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"310 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An international core outcome set for primary progressive aphasia (COS-PPA): Consensus-based recommendations for communication interventions across research and clinical settings","authors":"Anna Volkmer, Emily Viega Alves, Hagit Bar-Zeev, Elena Barbieri, Petronilla Battista, Ashleigh Beales, Barbara Costa Beber, Emilie Brotherhood, Ines Ribeiro Cadorio, Maria Teresa Carthery-Goulart, Jade Cartwright, Sebastian Crutch, Karen Croot, Maria Isabel d´Ávila Freitas, Jeanne Gallée, Stephanie M. Grasso, Katarina Haley, Heleen Hendriksen, Shalom Henderson, Lize Jiskoot, Isabel Junqueira Almeida, Jackie Kindell, Rachel Kingma, Lorinda LY Kwan-Chen, Monica Lavoie, Adi Lifshitz-Ben-Basat, Regina Jokel, Aurore Mahut-Dubos, Jordi A. Matias-Guiu, Michèle Masson-Trottier, Marcus Meinzer, Ellen McGowan, Carolina Mendez-Orellana, Aaron M. Meyer, Carly Millanski, Núria Montagut, Aimee Mooney, Darby J. Morhardt, Lyndsey Nickels, Monica Norvik, Iris Edda Nowenstein, Avanthi Paplikar, Margaret Pozzebon, Antoine Renard, Leanne Ruggero, Emily Rogalski, Anna U. Rysop, Fredrik Sand Aronsson, Aida Suárez-González, Sharon Savage, Mai Tran Thi, Kyriana Tsapkini, Cathleen Taylor-Rubin, Donna C. Tippett, Nina Unger, Lizet van Ewijk, Sandra Wielaert, Ingvild Elisabeth Winsnes, Anne Whitworth, Ibrahim Can Yasa, David Copland, Maya L. Henry, Jason D. Warren, Rosemary Varley, Sarah J. Wallace, Chris J. D. Hardy","doi":"10.1002/alz.14362","DOIUrl":"https://doi.org/10.1002/alz.14362","url":null,"abstract":"Interventions to treat speech-language difficulties in primary progressive aphasia (PPA) often use word accuracy as a highly comparable outcome. However, there are more constructs of importance to people with PPA that have received less attention.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"80 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thorase deficiency causes both Aβ accumulation and tau hyperphosphorylation in mouse brain","authors":"Han Zhang, Menghua Cai, Fei Gao, Jia Yang, Chao Li, Jingyi Han, Yue Wang, Yi Xu, Yu Hu, Hui Chen, Wei He, Jianmin Zhang","doi":"10.1002/alz.14329","DOIUrl":"https://doi.org/10.1002/alz.14329","url":null,"abstract":"The pathogenesis of two major pathogenic characters—amyloid beta (Aβ) accumulation and hyperphosphorylated tau protein—in the brains of patients with Alzheimer's disease (AD) remains unclear.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"20 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The case for regulatory approval of amyloid-lowering immunotherapies in Alzheimer's disease based on clearcut biomarker evidence","authors":"Paul Aisen, Randall J. Bateman, Damian Crowther, Jeff Cummings, John Dwyer, Takeshi Iwatsubo, Marie Kosco-Vilbois, Eric McDade, Richard Mohs, Philip Scheltens, Reisa Sperling, Dennis Selkoe","doi":"10.1002/alz.14342","DOIUrl":"https://doi.org/10.1002/alz.14342","url":null,"abstract":"Decades of research have provided evidence that Alzheimer's disease (AD) is caused in part by cerebral accumulation of amyloid beta-protein (Aβ). In 2023, the US Food and Drug Administration gave full regulatory approval to a disease-modifying Aβ antibody for early AD. Secondary prevention trials with Aβ antibodies are underway. We summarize peer-reviewed evidence for targeting Aβ and argue that regulators should consider approving new agents working by similar mechanisms (Aβ antibodies and vaccines) based on robust amyloid lowering and reasonable safety. The urgent need to provide treatments to millions of mildly symptomatic patients suggests that AD should join other diseases for which standard approval is based on significant changes in mechanistically meaningful biomarkers coupled with safety. Robust amyloid lowering in secondary prevention trials of people who have amyloid plaques but are asymptomatic could also provide evidence of a change in the pathophysiological progression of AD as a basis for regulatory approval.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"3 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetics of dementia remains unraveled in Latin American and Caribbean populations: A call for collaborative efforts","authors":"Ariel Caviedes, Paulina Orellana, Cristian Ávila-Rincón, Agustín Ibáñez, Michael J. Corley, Hernando Santamaría-García, Claudia Duran-Aniotz, Carolina Ochoa-Rosales","doi":"10.1002/alz.14295","DOIUrl":"https://doi.org/10.1002/alz.14295","url":null,"abstract":"<p>Dementia is a major health issue in Latin America and the Caribbean (LAC), with a prevalence of 9.5% and an incidence of 26.0 per 1000 among people over 60 years. With cases expected to triple by 2050, there is an urgent need for more extensive local research in this field.<span><sup>1</sup></span> Despite advancements in neuroimaging and protein biomarkers, significant gaps remain in understanding how biological mechanisms that interact with LAC-specific environmental exposures influence dementia risk, presentation, and treatment. Interactions between genetic and environmental factors, mainly through epigenetic changes including DNA methylation (DNAm), noncoding RNA, and histone modifications, can modulate gene expression, altering molecular traits and health outcomes.<span><sup>2</sup></span> Adverse environmental exposures in LAC, including socioeconomic disparities, pollutants, unhealthy habits, and comorbidities, have been associated with higher dementia risk,<span><sup>1</sup></span> potentially through epigenetic mechanisms. Most existing knowledge on epigenetics is derived from studies conducted in Europe and the United States, which limits the generalization of these findings to underrepresented regions,<span><sup>3</sup></span> including LAC. To understand state-of-the-art epigenetic studies on dementia in LAC, we conducted a systematic review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) protocols. Our search focused on chemical modifications of the DNA or histones able to regulate chromatin's structure. We reviewed the literature up to May 2024 in MEDLINE, Web of Science, PubMed, and Scopus databases (research strategy and findings in Table 1). Surprisingly, we found only five case-control studies comparing late-onset Alzheimer's disease (LOAD)<span><sup>4-6</sup></span> or mild cognitive impairment (MCI)<span><sup>7, 8</sup></span> versus healthy controls, revealing a disparity in published studies on epigenetics and dementia in LAC. Further epigenetics research is needed in the region, including the use of cutting-edge methods, target tissues, and systematic approaches. Studies have investigated global DNAm (<i>LINE-1</i>).<span><sup>4</sup></span> DNAm in candidate genes.<span><sup>5, 6</sup></span> or genome-wide DNAm<span><sup>7, 8</sup></span> assessed in peripheral blood. Two studies were conducted in Colombian,<span><sup>4, 5</sup></span> two in Mexican-American (MA),<span><sup>7, 8</sup></span> and one in Costa Rican populations.<span><sup>6</sup></span> Three studies addressed sex<span><sup>4, 5</sup></span> or ethnic<span><sup>8</sup></span> differences in DNAm. The study conducted by Hernández et al. found no significant differences in <i>LINE-1</i> methylation across LOAD patients and controls, even after stratification by sex or <i>APOE4</i> genotypes.<span><sup>4</sup></span> Further, Salcedo-Tacuma et al. identified significantly lower DNAm levels at three CpGs at <i>BIN1<","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"72 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated cerebellar radiomic-network model for predicting mild cognitive impairment in Alzheimer's disease","authors":"Yini Chen, Yiwei Qi, Yiying Hu, Xinhui Qiu, Tao Qiu, Song Li, Meichen Liu, Qiqi Jia, Bo Sun, Cong Liu, Tianbai Li, Weidong Le","doi":"10.1002/alz.14361","DOIUrl":"https://doi.org/10.1002/alz.14361","url":null,"abstract":"Pathological and neuroimaging alterations in the cerebellum of Alzheimer's disease (AD) patients have been documented. However, the role of cerebellum-derived radiomic and structural connectome modeling in the prediction of AD progression remains unclear.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"34 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific topological structure associated with dementia via latent space estimation","authors":"Selena Wang, Yiting Wang, Frederick H. Xu, Xinyuan Tian, Carolyn A. Fredericks, Li Shen, Yize Zhao","doi":"10.1002/alz.14266","DOIUrl":"https://doi.org/10.1002/alz.14266","url":null,"abstract":"We investigate sex-specific topological structures associated with typical Alzheimer's disease (AD) dementia using a novel state-of-the-art latent space estimation technique.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"7 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacodynamic effects of semorinemab on plasma and CSF biomarkers of Alzheimer's disease pathophysiology","authors":"Stephen P. Schauer, Balazs Toth, Julie Lee, Lee A. Honigberg, Vidya Ramakrishnan, Jenny Jiang, Gwendlyn Kollmorgen, Anna Bayfield, Norbert Wild, Jennifer Hoffman, Ryan Ceniceros, Michael Dolton, Sandra M. Sanabria Bohórquez, Casper C. Hoogenraad, Kristin R. Wildsmith, Edmond Teng, Cecilia Monteiro, Veronica Anania, Felix L. Yeh","doi":"10.1002/alz.14346","DOIUrl":"https://doi.org/10.1002/alz.14346","url":null,"abstract":"INTRODUCTIONSemorinemab, an anti‐tau monoclonal antibody, was assessed in two Phase II trials for Alzheimer's disease (AD). Plasma and cerebrospinal fluid (CSF) biomarkers provided insights into the drug's potential mechanism of action.METHODSQualified assays were used to measure biomarkers of tau, amyloidosis, glial activity, neuroinflammation, synaptic function, and neurodegeneration from participant samples in Tauriel (NCT03289143) and Lauriet (NCT03828747) Phase II trials.RESULTSPlasma phosphorylated Tau 181 (pTau181) and CSF chitinase‐3‐like protein 1 (YKL‐40) increased following semorinemab treatment in both studies. In Lauriet, increasing plasma glial fibrillary protein (GFAP) concentrations stabilized with semorinemab, while this was not observed in Tauriel. Other AD pathophysiology biomarkers showed no consistent response to semorinemab.DISCUSSIONIncreases in CSF YKL‐40 suggest that semorinemab may stimulate microglia activation in the presence of AD‐associated Tau pathology, but not in healthy controls. Stabilization of plasma GFAP in Lauriet indicates a possible impact on reactive gliosis in mild‐to‐moderate AD.Trial Registration: Tauriel ClinicalTrials.gov Identifier: NCT03289143. Lauriet ClinicalTrials.gov Identifier: NCT03828747. Phase 1 ClinicalTrials.gov Identifier: NCT02820896.Highlights<jats:list list-type=\"bullet\"> <jats:list-item>AD pathophysiology biomarkers were measured to assess the mechanism of action.</jats:list-item> <jats:list-item>Semorinemab increased CSF YKL‐40 in participants with AD but not in healthy controls.</jats:list-item> <jats:list-item>Semorinemab possibly stabilized plasma GFAP in the Lauriet trial.</jats:list-item> <jats:list-item>Semorinemab treatment may activate microglia and moderate reactive gliosis.</jats:list-item> </jats:list>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"1 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}