ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2023
The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort.
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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 35 citations in OpenAlex.
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- Alterations of the brain functional organization in young-onset Alzheimer's disease: Is it a matter of "time"?Journal of Alzheimer's disease : JAD · 2025Article
- Biological age acceleration in Alzheimer's disease modulates relative cortical to medial temporal lobe neurodegeneration.Neurobiology of aging · 2025Article
- Neural mechanisms of disease pathology and cognition in young-onset Alzheimer's disease variants.Journal of Alzheimer's disease : JAD · 2025Article
- Default mode network tau predicts future clinical decline in atypical early Alzheimer's disease.Brain : a journal of neurology · 2025Article
- Characterizing and validating 12-month reliable cognitive change in Early-Onset Alzheimer's Disease for use in clinical trials.The journal of prevention of Alzheimer's disease · 2025Article
- Heterogeneous clinical phenotypes of sporadic early-onset Alzheimer's disease: a neuropsychological data-driven approach.Alzheimer's research & therapy · 2025Article
- Female sex is linked to a stronger association between sTREM2 and CSF p-tau in Alzheimer's disease.EMBO molecular medicine · 2025Article
- Voiceprints of cognitive impairment: analyzing digital voice for early detection of Alzheimer's and related dementias.NPJ dementia · 2025Article
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Authors and funding
50 authors at 20 institutions in 1 country.
Alexandra TouroutoglouDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Yuta KatsumiDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Michael BrickhouseDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Alexander ZaitsevDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Ryan EckboDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Paul AisenAlzheimer's Therapeutic Research Institute, University of Southern California, San Diego, California, USA.
Laurel BeckettDepartment of Public Health Sciences, University of California - Davis, Davis, California, USA.
Jeffrey L DageDepartment of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Ani EloyanDepartment of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island, USA.
Tatiana ForoudDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Bernardino GhettiDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Percy GriffinMedical & Scientific Relations Division, Alzheimer's Association, Chicago, Illinois, USA.
Dustin HammersDepartment of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Clifford R JackDepartment of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Joel H KramerDepartment of Neurology, University of California - San Francisco, San Francisco, California, USA.
Leonardo IaccarinoDepartment of Neurology, University of California - San Francisco, San Francisco, California, USA.
Renaud La JoieDepartment of Neurology, University of California - San Francisco, San Francisco, California, USA.
Nidhi S MundadaDepartment of Neurology, University of California - San Francisco, San Francisco, California, USA.
Robert KoeppeDepartment of Radiology, University of Michigan, Ann Arbor, Michigan, USA.
Walter A KukullDepartment of Epidemiology, University of Washington, Seattle, Washington, USA.
Melissa E MurrayDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Kelly NudelmanDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Angelina J PolsinelliDepartment of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Malia RumbaughDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
David N Soleimani-MeigooniDepartment of Neurology, University of California - San Francisco, San Francisco, California, USA.
Arthur TogaLaboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Los Angeles, California, USA.
Prashanthi VemuriDepartment of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Alireza AtriBanner Sun Health Research Institute, Sun City, Arizona, USA.
Gregory S DayDepartment of Neurology, Mayo Clinic in Florida, Jacksonville, Florida, USA.
Ranjan DuaraWien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami, Florida, USA.
Neill R Graff-RadfordDepartment of Neurology, Mayo Clinic in Florida, Jacksonville, Florida, USA.
Lawrence S HonigTaub Institute and Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
David T JonesDepartment of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Joseph C MasdeuNantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, Texas, USA.
Mario F MendezDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Erik MusiekDepartment of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.
Chiadi U OnyikeDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Meghan RiddleDepartment of Neurology, Alpert Medical School, Brown University, Providence, Rhode Island, USA.
Emily RogalskiDepartment of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Stephen SallowayDepartment of Neurology, Alpert Medical School, Brown University, Providence, Rhode Island, USA.
Sharon ShaDepartment of Neurology & Neurological Sciences, Stanford University, Palo Alto, California, USA.
R Scott TurnerDepartment of Neurology, Georgetown University, Washington, D.C., USA.
Thomas S WingoDepartment of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
David A WolkDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Kyle WomackDepartment of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.
Maria C CarrilloMedical & Scientific Relations Division, Alzheimer's Association, Chicago, Illinois, USA.
Gil D RabinoviciDepartment of Neurology, University of California - San Francisco, San Francisco, California, USA.
Liana G ApostolovaDepartment of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Bradford C DickersonDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
LEADS Consortium
Indiana University School of MedicineUniversity of California, San Francisco · USMassachusetts General Hospital · USBrown University · USMayo Clinic · USAlzheimer's Association · USJacksonville College · USWashington University in St. Louis · USBanner Sun Health Research Institute · USColumbia University Irving Medical Center · USEmory University · USGeorgetown University · USHarvard University · USHouston Methodist · USIndiana University – Purdue University Indianapolis · USJohns Hopkins University · USKeck Hospital of USC · USMayo Clinic in Florida · USMount Sinai Medical Center · USNorthwestern University · US
Funding
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8MEarly Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3MNational Alzheimer's Coordinating CenterU24AG072122 · NIA · UNIVERSITY OF WASHINGTON · PI STEPHENS, KARI A · 2021 to 2025
$45.8MTHE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI BETENSKY, REBECCA A. · 1985 to 2018
$42.1MResearch Education ComponentP30AG010133 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 1991 to 2020
$37.3MResearch Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Serggio Carlo Lanata · 2019 to 2026
$36.9MResearch Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5MResearch Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI Walter K. Kremers · 2019 to 2026
$33.5MResearch Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Andrew Franklin Teich · 2020 to 2026
$30.1MResearch Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI Corinne Pettigrew · 2020 to 2026
$29.3MThe Goizueta Alzheimer's Disease Research CenterP30AG066511 · NIA · EMORY UNIVERSITY · PI Amy D Rodriguez · 2020 to 2026
$29.0MStanford Alzheimer's Disease Research CenterAdmin Supp: Developing iPSC models for AD and PDP30AG066515 · NIA · STANFORD UNIVERSITY · PI Jennifer Kaci Fairchild · 2020 to 2026
$29.0MNCRR NIH HHS S10 RR021110NCRR NIH HHS S10 RR023043NCRR NIH HHS S10 RR023401NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG072976NIA NIH HHS P30 AG072977NIA NIH HHS P30 AG072979NIA NIH HHS P30 AG072980NIA NIH HHS P50 AG005134NIA NIH HHS R21 AG073744NIA NIH HHS R56 AG057195NIA NIH HHS U01 AG057195NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG072122NIBIB NIH HHS P41 EB015896NIDCD NIH HHS K23 DC016912NIDCD NIH HHS R01 DC014296NIDCD NIH HHS R21 DC019567NIH HHS
Abstract
introductionMagnetic resonance imaging (MRI) research has advanced our understanding of neurodegeneration in sporadic early-onset Alzheimer's disease (EOAD) but studies include small samples, mostly amnestic EOAD, and have not focused on developing an MRI biomarker.
methodsWe analyzed MRI scans to define the sporadic EOAD-signature atrophy in a small sample (n = 25) of Massachusetts General Hospital (MGH) EOAD patients, investigated its reproducibility in the large longitudinal early-onset Alzheimer's disease study (LEADS) sample (n = 211), and investigated the relationship of the magnitude of atrophy with cognitive impairment.
resultsThe EOAD-signature atrophy was replicated across the two cohorts, with prominent atrophy in the caudal lateral temporal cortex, inferior parietal lobule, and posterior cingulate and precuneus cortices, and with relative sparing of the medial temporal lobe. The magnitude of EOAD-signature atrophy was associated with the severity of cognitive impairment. DISCUSSION: The EOAD-signature atrophy is a reliable and clinically valid biomarker of AD-related neurodegeneration that could be used in clinical trials for EOAD. HIGHLIGHTS: We developed an early-onset Alzheimer's disease (EOAD)-signature of atrophy based on magnetic resonance imaging (MRI) scans. EOAD signature was robustly reproducible across two independent patient cohorts. EOAD signature included prominent atrophy in parietal and posterior temporal cortex. The EOAD-signature atrophy was associated with the severity of cognitive impairment. EOAD signature is a reliable and clinically valid biomarker of neurodegeneration.
Indexed as
Alzheimer DiseaseAtrophyBiomarkersHumansMagnetic Resonance ImagingReproducibility of ResultsTemporal LobeBiomarkersdisease signatureearly-onset Alzheimer's diseasemagnetic resonance imaging (MRI)
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