Wassim Elyaman, Lawrence J. Stern, Ning Jiang, Dallin Dressman, Philip Bradley, David Klatzmann, Elizabeth M. Bradshaw, Donna L. Farber, Sally C. Kent, Shahab Chizari, Kristen Funk, Davangere Devanand, Kiran T. Thakur, Towfique Raj, Osama Al Dalahmah, Rani A. Sarkis, Howard L. Weiner, Neil A. Shneider, Serge Przedborski
This proceedings article summarizes the inaugural “T Cells in the Brain” symposium held at Columbia University. Experts gathered to explore the role of T cells in neurodegenerative diseases. Key topics included characterization of antigen-specific immune responses, T cell receptor (TCR) repertoire, microbial etiology in Alzheimer's disease (AD), and microglia–T cell crosstalk, with a focus on how T cells affect neuroinflammation and AD biomarkers like amyloid beta and tau. The symposium also examined immunotherapies for AD, including the Valacyclovir Treatment of Alzheimer's Disease (VALAD) trial, and two clinical trials leveraging regulatory T cell approaches for multiple sclerosis and amyotrophic lateral sclerosis therapy. Additionally, single-cell RNA/TCR sequencing of T cells and other immune cells provided insights into immune dynamics in neurodegenerative diseases. This article highlights key findings from the symposium and outlines future research directions to further understand the role of T cells in neurodegeneration, offering innovative therapeutic approaches for AD and other neurodegenerative diseases.
{"title":"Exploring the role of T cells in Alzheimer's and other neurodegenerative diseases: Emerging therapeutic insights from the T Cells in the Brain symposium","authors":"Wassim Elyaman, Lawrence J. Stern, Ning Jiang, Dallin Dressman, Philip Bradley, David Klatzmann, Elizabeth M. Bradshaw, Donna L. Farber, Sally C. Kent, Shahab Chizari, Kristen Funk, Davangere Devanand, Kiran T. Thakur, Towfique Raj, Osama Al Dalahmah, Rani A. Sarkis, Howard L. Weiner, Neil A. Shneider, Serge Przedborski","doi":"10.1002/alz.14548","DOIUrl":"https://doi.org/10.1002/alz.14548","url":null,"abstract":"This proceedings article summarizes the inaugural “T Cells in the Brain” symposium held at Columbia University. Experts gathered to explore the role of T cells in neurodegenerative diseases. Key topics included characterization of antigen-specific immune responses, T cell receptor (TCR) repertoire, microbial etiology in Alzheimer's disease (AD), and microglia–T cell crosstalk, with a focus on how T cells affect neuroinflammation and AD biomarkers like amyloid beta and tau. The symposium also examined immunotherapies for AD, including the Valacyclovir Treatment of Alzheimer's Disease (VALAD) trial, and two clinical trials leveraging regulatory T cell approaches for multiple sclerosis and amyotrophic lateral sclerosis therapy. Additionally, single-cell RNA/TCR sequencing of T cells and other immune cells provided insights into immune dynamics in neurodegenerative diseases. This article highlights key findings from the symposium and outlines future research directions to further understand the role of T cells in neurodegeneration, offering innovative therapeutic approaches for AD and other neurodegenerative diseases.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"119 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044416","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}
Salma Elasfar, Hajr Hameed, Bradley F. Boeve, Julie A. Fields, Clifford R. Jack Jr., Kejal Kantarci, Erik K. St. Louis, Val J. Lowe, Ronald C. Petersen, Farwa Ali, Kaylena Ehgoetz Martens
INTRODUCTION
We aimed to compare gait between individuals with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and cognitively unimpaired (CU) individuals and to evaluate the association between gait and regional amyloid beta (Aβ) burden in AD and DLB.
METHODS
We included 420 participants (70 AD, 70 DLB, 280 CU) in the Mayo Clinic Study of Aging (MCSA). Gait was assessed using a pressure-sensor walkway. Aβ deposition was analyzed with Pittsburgh compound B (PiB) positron emission topography (PET).
RESULTS
The DLB group had reduced stride velocity, step length, and stride width variability, as well as increased double support percentage (%DS) and variability in step length, swing time, and step time compared to the AD and CU groups. Aβ burden was not associated with any gait outcomes.
DISCUSSION
This study provides additional evidence that gait differs between AD and DLB. Larger studies are needed to investigate associations between Aβ burden and gait outcomes in dementia.
Highlights
Gait was more impaired in dementia than in cognitively unimpaired (CU) controls.
Compared with Alzheimer's disease (AD), Dementia with Lewy bodies (DLB) had more impaired pace, variability, and postural control.
Step length and double support (%) distinguished DLB and AD with moderate accuracy.
{"title":"Identifying gait differences between Alzheimer's disease and dementia with Lewy bodies and their associations with regional amyloid deposition","authors":"Salma Elasfar, Hajr Hameed, Bradley F. Boeve, Julie A. Fields, Clifford R. Jack Jr., Kejal Kantarci, Erik K. St. Louis, Val J. Lowe, Ronald C. Petersen, Farwa Ali, Kaylena Ehgoetz Martens","doi":"10.1002/alz.14351","DOIUrl":"10.1002/alz.14351","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We aimed to compare gait between individuals with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and cognitively unimpaired (CU) individuals and to evaluate the association between gait and regional amyloid beta (Aβ) burden in AD and DLB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We included 420 participants (70 AD, 70 DLB, 280 CU) in the Mayo Clinic Study of Aging (MCSA). Gait was assessed using a pressure-sensor walkway. Aβ deposition was analyzed with Pittsburgh compound B (PiB) positron emission topography (PET).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The DLB group had reduced stride velocity, step length, and stride width variability, as well as increased double support percentage (%DS) and variability in step length, swing time, and step time compared to the AD and CU groups. Aβ burden was not associated with any gait outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study provides additional evidence that gait differs between AD and DLB. Larger studies are needed to investigate associations between Aβ burden and gait outcomes in dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Gait was more impaired in dementia than in cognitively unimpaired (CU) controls.</li>\u0000 \u0000 <li>Compared with Alzheimer's disease (AD), Dementia with Lewy bodies (DLB) had more impaired pace, variability, and postural control.</li>\u0000 \u0000 <li>Step length and double support (%) distinguished DLB and AD with moderate accuracy.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044350","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}
Malnutrition correlates with neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD); however, the potential mechanism underlying this association remains unclear.
{"title":"Malnutrition exacerbating neuropsychiatric symptoms on the Alzheimer's continuum is relevant to the cAMP signaling pathway: Human and mouse studies","authors":"Jiwei Jiang, Tianlin Jiang, Xiaohong Wang, Min Zhao, Hanping Shi, Huiying Zhang, Wenyi Li, Shirui Jiang, Xiaoli Zhang, Jiawei Zhou, Qiwei Ren, Linlin Wang, Shiyi Yang, Zeshan Yao, Yaou Liu, Jun Xu","doi":"10.1002/alz.14506","DOIUrl":"https://doi.org/10.1002/alz.14506","url":null,"abstract":"Malnutrition correlates with neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD); however, the potential mechanism underlying this association remains unclear.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"2 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044259","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}
Andre Fischer, Kwangsik Nho, Andrew J. Saykin, Ivana Delalle
Dear Editor,
We are truly grateful for the positive and thoughtful feedback on our recent studies exploring microRNAs (miRNAs) as biomarkers for Alzheimer's disease (AD).1 It is encouraging to see our work recognized for its potential contribution to the field of AD research.
We fully agree that replication is crucial. Although our findings highlight promising miRNA signatures, validating these results in independent cohorts will be key to solidifying their potential clinical relevance. We are confident that future studies will build upon these insights, further advancing the development of reliable biomarkers for early diagnosis and progression tracking. In addition, we would like to highlight the potential of miRNAs in identifying the different molecular and cellular phases of AD pathogenesis.
We also appreciate the remarks on the clinical utility of miRNA measurements. As the field evolves, demonstrating the added value of miRNAs alongside established biomarkers remains a priority. We are optimistic that ongoing and future research will help establish miRNAs as complementary tools for improving diagnostic precision.
The notion of miRNA-based therapies is particularly exciting. Although this was not the primary focus of our current studies, we agree that stratified RNA therapies hold immense promise as future therapeutic strategies. In AD research, it will be key to treat the right patient at the right time with the right therapeutic approach. The ability to modify miRNA levels in a targeted manner opens new avenues for addressing the different pathological phases in AD, and we look forward to contributing to this research.
In conclusion, we are delighted by the recognition of our work and are eager to continue exploring these important questions as the field progresses. We sincerely appreciate the constructive dialogue and look forward to further advancing this exciting area of research.
A. Fisher, K. Nho, A.J. Saykin, and I. Delalle
{"title":"Response to the Letter, “Circulating small RNAs shed light on dementia risk,” by Anthony S. Zannas","authors":"Andre Fischer, Kwangsik Nho, Andrew J. Saykin, Ivana Delalle","doi":"10.1002/alz.14404","DOIUrl":"https://doi.org/10.1002/alz.14404","url":null,"abstract":"<p>Dear Editor,</p>\u0000<p>We are truly grateful for the positive and thoughtful feedback on our recent studies exploring microRNAs (miRNAs) as biomarkers for Alzheimer's disease (AD).<span><sup>1</sup></span> It is encouraging to see our work recognized for its potential contribution to the field of AD research.</p>\u0000<p>We fully agree that replication is crucial. Although our findings highlight promising miRNA signatures, validating these results in independent cohorts will be key to solidifying their potential clinical relevance. We are confident that future studies will build upon these insights, further advancing the development of reliable biomarkers for early diagnosis and progression tracking. In addition, we would like to highlight the potential of miRNAs in identifying the different molecular and cellular phases of AD pathogenesis.</p>\u0000<p>We also appreciate the remarks on the clinical utility of miRNA measurements. As the field evolves, demonstrating the added value of miRNAs alongside established biomarkers remains a priority. We are optimistic that ongoing and future research will help establish miRNAs as complementary tools for improving diagnostic precision.</p>\u0000<p>The notion of miRNA-based therapies is particularly exciting. Although this was not the primary focus of our current studies, we agree that stratified RNA therapies hold immense promise as future therapeutic strategies. In AD research, it will be key to treat the right patient at the right time with the right therapeutic approach. The ability to modify miRNA levels in a targeted manner opens new avenues for addressing the different pathological phases in AD, and we look forward to contributing to this research.</p>\u0000<p>In conclusion, we are delighted by the recognition of our work and are eager to continue exploring these important questions as the field progresses. We sincerely appreciate the constructive dialogue and look forward to further advancing this exciting area of research.</p>\u0000<p>A. Fisher, K. Nho, A.J. Saykin, and I. Delalle</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"15 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044349","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}
Marieke P. Hoevenaar-Blom, Jason Shourik, Jan Willem van Dalen, Willem A. van Gool, Sandrine Andrieu, Edo Richard, Nicola Coley, Eric Moll van Charante,
We explored which dementia risk factors in two multidomain prevention trials mediate beneficial, neutral, or counteracting effects on dementia incidence.
{"title":"Mediation of modifiable risk factors in two multidomain dementia prevention trials","authors":"Marieke P. Hoevenaar-Blom, Jason Shourik, Jan Willem van Dalen, Willem A. van Gool, Sandrine Andrieu, Edo Richard, Nicola Coley, Eric Moll van Charante, ","doi":"10.1002/alz.14557","DOIUrl":"https://doi.org/10.1002/alz.14557","url":null,"abstract":"We explored which dementia risk factors in two multidomain prevention trials mediate beneficial, neutral, or counteracting effects on dementia incidence.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"7 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044728","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}
Mythily Subramaniam, Edimansyah Abdin, PV Asharani, Kumarasan Roystonn, Fiona Devi, Wang Peizhi, Saleha Shafie, Vathsala Sagayadevan, Anitha Jeyagurunathan, Boon Yiang Chua, Bernard Tan, Janhavi Ajit Vaingankar, Fengyuan Yao, Harish Magadi, Stefan Ma, Wai Leng Chow, Paul McCrone, Derrick Heng, Rathi Mahendran, Martin Prince, Li Ling Ng, Siow Ann Chong
The study aimed to assess changes in the prevalence of dementia in Singapore over the past decade.
{"title":"Prevalence of dementia in Singapore: Changes across a decade","authors":"Mythily Subramaniam, Edimansyah Abdin, PV Asharani, Kumarasan Roystonn, Fiona Devi, Wang Peizhi, Saleha Shafie, Vathsala Sagayadevan, Anitha Jeyagurunathan, Boon Yiang Chua, Bernard Tan, Janhavi Ajit Vaingankar, Fengyuan Yao, Harish Magadi, Stefan Ma, Wai Leng Chow, Paul McCrone, Derrick Heng, Rathi Mahendran, Martin Prince, Li Ling Ng, Siow Ann Chong","doi":"10.1002/alz.14485","DOIUrl":"https://doi.org/10.1002/alz.14485","url":null,"abstract":"The study aimed to assess changes in the prevalence of dementia in Singapore over the past decade.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"58 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044348","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}
Luisa Sophie Schneider, Silka Dawn Freiesleben, Gerard van Breukelen, Xiao Wang, Frederic Brosseron, Michael T. Heneka, Stefan Teipel, Luca Kleineidam, Melina Stark, Nina Roy-Kluth, Michael Wagner, Annika Spottke, Matthias Schmid, Sandra Roeske, Christoph Laske, Matthias H. Munk, Robert Perneczky, Boris-Stephan Rauchmann, Katharina Buerger, Daniel Janowitz, Emrah Düzel, Wenzel Glanz, Frank Jessen, Ayda Rostamzadeh, Jens Wiltfang, Claudia Bartels, Ingo Kilimann, Anja Schneider, Klaus Fliessbach, Josef Priller, Eike Jakob Spruth, Julian Hellmann-Regen, Oliver Peters
The beneficial effects of amyloid beta 1-38, or Aβ(1-38), on Alzheimer's disease (AD) progression in humans in vivo remain controversial. We investigated AD patients' cerebrospinal fluid (CSF) Aβ(1-38) and AD progression.
{"title":"Linking higher amyloid beta 1-38 (Aβ(1-38)) levels to reduced Alzheimer's disease progression risk","authors":"Luisa Sophie Schneider, Silka Dawn Freiesleben, Gerard van Breukelen, Xiao Wang, Frederic Brosseron, Michael T. Heneka, Stefan Teipel, Luca Kleineidam, Melina Stark, Nina Roy-Kluth, Michael Wagner, Annika Spottke, Matthias Schmid, Sandra Roeske, Christoph Laske, Matthias H. Munk, Robert Perneczky, Boris-Stephan Rauchmann, Katharina Buerger, Daniel Janowitz, Emrah Düzel, Wenzel Glanz, Frank Jessen, Ayda Rostamzadeh, Jens Wiltfang, Claudia Bartels, Ingo Kilimann, Anja Schneider, Klaus Fliessbach, Josef Priller, Eike Jakob Spruth, Julian Hellmann-Regen, Oliver Peters","doi":"10.1002/alz.14545","DOIUrl":"https://doi.org/10.1002/alz.14545","url":null,"abstract":"The beneficial effects of amyloid beta 1-38, or Aβ(1-38), on Alzheimer's disease (AD) progression in humans in vivo remain controversial. We investigated AD patients' cerebrospinal fluid (CSF) Aβ(1-38) and AD progression.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044346","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}
Jr-Jiun Liou, Jerry Lou, Lisi Flores-Aguilar, Jamie Nakagiri, William Yong, Christy L. Hom, Eric W. Doran, Minodora O. Totoiu, Ira Lott, Mark Mapstone, David B. Keator, Adam M. Brickman, Sierra T. Wright, Brittany Nelson, Florence Lai, Laura Xicota, Lam-Ha T. Dang, Jinghang Li, Tales Santini, Joseph M. Mettenburg, Milos D. Ikonomovic, Julia Kofler, Tamer Ibrahim, Elizabeth Head
Aging adults with Down syndrome (DS) accumulate Alzheimer's disease (AD) neuropathology, including amyloid beta plaques and neurofibrillary tangles, by age 40.
{"title":"A neuropathology case report of a woman with Down syndrome who remained cognitively stable: Implications for resilience to neuropathology","authors":"Jr-Jiun Liou, Jerry Lou, Lisi Flores-Aguilar, Jamie Nakagiri, William Yong, Christy L. Hom, Eric W. Doran, Minodora O. Totoiu, Ira Lott, Mark Mapstone, David B. Keator, Adam M. Brickman, Sierra T. Wright, Brittany Nelson, Florence Lai, Laura Xicota, Lam-Ha T. Dang, Jinghang Li, Tales Santini, Joseph M. Mettenburg, Milos D. Ikonomovic, Julia Kofler, Tamer Ibrahim, Elizabeth Head","doi":"10.1002/alz.14479","DOIUrl":"https://doi.org/10.1002/alz.14479","url":null,"abstract":"Aging adults with Down syndrome (DS) accumulate Alzheimer's disease (AD) neuropathology, including amyloid beta plaques and neurofibrillary tangles, by age 40.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"20 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044340","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}
<p>With populations aging worldwide, dementia has an enormous impact on individuals and societies. Alzheimer's disease (AD), the most common form of dementia, is currently estimated to afflict nearly seven million persons over age 65 in the United States, a number that could double in the coming decades.<span><sup>1</sup></span> Like every disease, the quest to prevent and treat dementia relies on the discovery of biomarkers,<span><sup>2</sup></span> quantifiable indicators that can aid the early risk prediction and disease diagnosis. Circulating (peripheral) molecular markers are particularly attractive candidates, given they can be easily accessed with minimally invasive procedures, allowing larger-scale applications to identify at-risk individuals. Yet a critical challenge is that circulating markers do not necessarily reflect pathological processes in the brain, the organ that plays a central role in dementia phenotypes.</p> <p>Addressing this challenge, two complementary studies published in <i>Alzheimer's & Dementia</i> leveraged data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to suggest the promise of blood plasma microRNAs (miRNAs) as AD biomarkers. The first study assessed the diagnostic potential of a total of 300 miRNAs across 803 age- and gender-matched ADNI participants classified as controls or as having early mild cognitive impairment (MCI), late MCI, or AD.<span><sup>3</sup></span> Findings showed that a composite signature consisting of three miRNAs could distinguish diagnoses at baseline and further predict the longitudinal (12-year) conversion of MCI to dementia with an accuracy comparable to or better than that of central biomarkers and clinical screening. The second study aimed to identify plasma miRNAs dysregulated in association with central AD biomarkers measured in ADNI participants’ cerebrospinal fluid (CSF).<span><sup>4</sup></span> A total of 17 unique plasma miRNAs were found to be differentially expressed in association with established amyloid (Aβ1-42), tau (total-tau), and neurodegeneration (p-tau181) CSF markers. By performing pathway analyses of the miRNA-targeted genes, the two studies further showed that several molecular pathways were enriched in diagnostic groups and in association with central biomarkers. Key enriched pathways involved various dementia-related processes, including inflammatory signaling, cognitive processes, mitochondria function, cell migration, and neuronal projection. Together, these observations support circulating miRNAs as promising AD biomarkers and further suggest underlying biological processes through which the miRNA regulome may contribute to dementia risk.</p> <p>Moreover, the foregoing observations have broader implications for research aiming to understand dementia risk and promote biomarker discovery. Most dementias are thought to result from a complex interplay between genetic and environmental factors,<span><sup>5</sup></span> and epigenetic mechanisms a
{"title":"Circulating small RNAs shed new light on dementia risk","authors":"Anthony S. Zannas","doi":"10.1002/alz.14546","DOIUrl":"https://doi.org/10.1002/alz.14546","url":null,"abstract":"<p>With populations aging worldwide, dementia has an enormous impact on individuals and societies. Alzheimer's disease (AD), the most common form of dementia, is currently estimated to afflict nearly seven million persons over age 65 in the United States, a number that could double in the coming decades.<span><sup>1</sup></span> Like every disease, the quest to prevent and treat dementia relies on the discovery of biomarkers,<span><sup>2</sup></span> quantifiable indicators that can aid the early risk prediction and disease diagnosis. Circulating (peripheral) molecular markers are particularly attractive candidates, given they can be easily accessed with minimally invasive procedures, allowing larger-scale applications to identify at-risk individuals. Yet a critical challenge is that circulating markers do not necessarily reflect pathological processes in the brain, the organ that plays a central role in dementia phenotypes.</p>\u0000<p>Addressing this challenge, two complementary studies published in <i>Alzheimer's & Dementia</i> leveraged data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to suggest the promise of blood plasma microRNAs (miRNAs) as AD biomarkers. The first study assessed the diagnostic potential of a total of 300 miRNAs across 803 age- and gender-matched ADNI participants classified as controls or as having early mild cognitive impairment (MCI), late MCI, or AD.<span><sup>3</sup></span> Findings showed that a composite signature consisting of three miRNAs could distinguish diagnoses at baseline and further predict the longitudinal (12-year) conversion of MCI to dementia with an accuracy comparable to or better than that of central biomarkers and clinical screening. The second study aimed to identify plasma miRNAs dysregulated in association with central AD biomarkers measured in ADNI participants’ cerebrospinal fluid (CSF).<span><sup>4</sup></span> A total of 17 unique plasma miRNAs were found to be differentially expressed in association with established amyloid (Aβ1-42), tau (total-tau), and neurodegeneration (p-tau181) CSF markers. By performing pathway analyses of the miRNA-targeted genes, the two studies further showed that several molecular pathways were enriched in diagnostic groups and in association with central biomarkers. Key enriched pathways involved various dementia-related processes, including inflammatory signaling, cognitive processes, mitochondria function, cell migration, and neuronal projection. Together, these observations support circulating miRNAs as promising AD biomarkers and further suggest underlying biological processes through which the miRNA regulome may contribute to dementia risk.</p>\u0000<p>Moreover, the foregoing observations have broader implications for research aiming to understand dementia risk and promote biomarker discovery. Most dementias are thought to result from a complex interplay between genetic and environmental factors,<span><sup>5</sup></span> and epigenetic mechanisms a","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"22 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044345","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}
Jiangli Jin, Jiong Chen, Clémence Cavaillès, Kristine Yaffe, Joseph Winer, Laura Stankeviciute, Brendan P. Lucey, Xiao Zhou, Song Gao, Dantao Peng, Yue Leng
Sleep disturbances are associated with Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD), but the relationship between sleep architecture, particularly rapid eye movement (REM) sleep, and AD/ADRD biomarkers remains unclear.
{"title":"Association of rapid eye movement sleep latency with multimodal biomarkers of Alzheimer's disease","authors":"Jiangli Jin, Jiong Chen, Clémence Cavaillès, Kristine Yaffe, Joseph Winer, Laura Stankeviciute, Brendan P. Lucey, Xiao Zhou, Song Gao, Dantao Peng, Yue Leng","doi":"10.1002/alz.14495","DOIUrl":"https://doi.org/10.1002/alz.14495","url":null,"abstract":"Sleep disturbances are associated with Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD), but the relationship between sleep architecture, particularly rapid eye movement (REM) sleep, and AD/ADRD biomarkers remains unclear.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"20 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044704","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}
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