ReviewAlzheimer's & dementia : the journal of the Alzheimer's Association2023
Pathogenic variants in the Longitudinal Early-onset Alzheimer's Disease Study cohort.
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Review 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 20 papers.
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20citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- EOAD-Signature Atrophy Predicts Dementia in Early-Onset MCI due to Alzheimer Disease: An MRI-Based Prognostic Biomarker.Neurology · 2026Article
- Proteome-wide genetic study identified therapeutic targets for early-onset and late-onset Alzheimer's disease.International journal of surgery (London, England) · 2026Article
- Distinct Tau PET Dynamics in Early vs. Late Age-of-Onset Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- Tau topography subtypes account for clinical heterogeneity and longitudinal trajectories in early-onset Alzheimer's disease.Brain communications · 2026Article
- Alzheimer's disease polygenic risk in early- and late-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Systemic inflammation as a central player in the initiation and development of Alzheimer's disease.Immunity & ageing : I & A · 2025Review
- Amyloid PET in Sporadic Early- Versus Late-Onset Alzheimer's Disease: Comparison of the LEADS and ADNI Cohorts.Annals of neurology · 2025Article
- ApoE3 Christchurch and tau interaction as a protective mechanism against Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Predictive Accuracy of a Clinical Model for Carriage of Pathogenic/Likely Pathogenic Variants in Patients with Dementia and a Positive Family History at PUMCH.Biomedicines · 2025Article
- LMTK2 and CRB1 are two novel risk genes for Alzheimer's disease in Han Chinese.The journal of prevention of Alzheimer's disease · 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
- The Spectrum of Genetic Risk in Alzheimer Disease.Neurology. Genetics · 2025Review
- Highly sensitive early-onset Alzheimer's disease: a case report.Frontiers in psychology · 2025Article
- Differences in baseline cognitive performance between participants with early-onset and late-onset Alzheimer's disease: Comparison of LEADS and ADNI.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Voiceprints of cognitive impairment: analyzing digital voice for early detection of Alzheimer's and related dementias.NPJ dementia · 2025Article
- Psychosocial burdens in early- versus late-onset dementia: analysis of discrimination, stress, and loneliness in the All of Us Research Program.Innovation in aging · 2025Article
- Early- and Late-Onset Alzheimer's Disease: Two Sides of the Same Coin?Diseases (Basel, Switzerland) · 2024Review
- Identification of patients receiving amyloid-targeting therapies in observational studies using amyloid PET trajectories: Insights from LEADS.Alzheimer's & dementia (Amsterdam, Netherlands)Article
- Sex and ethnicity in early-onset Alzheimer's disease biomarkers and global function.Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Authors and funding
43 authors at 20 institutions in 1 country.
Kelly N H NudelmanDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Trever JacksonDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Malia RumbaughDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Ani EloyanDepartment of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island, USA.
Marco AbreuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Jeffrey L DageDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Casey SnoddyDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Kelley M FaberDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Tatiana ForoudDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Dustin B HammersDepartment of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
DIAN/DIAN-TU Clinical/Genetics CommitteeWashington University School of Medicine, St. Louis, Missouri, USA.
Alexander TauroneDepartment of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island, USA.
Maryanne ThangarajahDepartment of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island, 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.
Joel KramerDepartment 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.
Arthur W 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, 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, 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 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 J 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.
Maria C CarrilloMedical & Scientific Relations Division, Alzheimer's Association, Chicago, Illinois, USA.
Bradford C DickersonDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Gil D RabinoviciDepartment of Neurology, University of California - San Francisco, San Francisco, California, USA.
Liana G ApostolovaIndiana Alzheimer's Disease Research Center, Indianapolis, Indiana, USA.
LEADS Consortium
Indiana University – Purdue University Indianapolis · USBrown University · USIndiana University School of MedicineMayo Clinic in Florida · USMayo Clinic · USUniversity of California, San Francisco · USAlzheimer's Association · USBanner Sun Health Research Institute · USColumbia University Irving Medical Center · USCornell University · USEmory University · USGeorgetown University · USJohns Hopkins University · USMassachusetts General Hospital · USMount Sinai Medical Center · USNorthwestern University · USStanford University · USUniversity of California, Davis · USUniversity of California, Los Angeles · USUniversity of Michigan–Ann Arbor · 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
$119.8MNATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8MEarly Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3MImaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9MWASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1MSatellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3MNational Alzheimer's Coordinating CenterU24AG072122 · NIA · UNIVERSITY OF WASHINGTON · PI STEPHENS, KARI A · 2021 to 2025
$45.8M'T V ASSESSMENT - MEMORY DISORDERED PATIENTS'P50AG005146 · NIA · JOHNS HOPKINS UNIVERSITY · PI HUGANIR, RICHARD L · 1985 to 2019
$37.6MResearch 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
$36.5MUPenn ADCC Biomarker CoreP30AG010124 · NIA · UNIVERSITY OF PENNSYLVANIA · PI XIE, SHARON XIANGWEN · 1991 to 2020
$35.1MAlzheimer's Association AARG-22-926940Alzheimer's Association LDRFP-21-818464Alzheimer's Association LEADS GENETICS-19-639372NIA NIH HHS K23 AG064029NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG072976NIA NIH HHS P30 AG072979NIA NIH HHS P30 AG072980NIA NIH HHS P50 AG005146NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG023501NIA NIH HHS P50 AG025688NIA NIH HHS P50 AG047366NIA NIH HHS R56 AG057195NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG057195NIA NIH HHS U19 AG032438NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG072122NIH HHS P30AG010124NIH HHS P30AG010133NIH HHS P30AG013854NIH HHS P30AG062421NIH HHS P30AG062422NIH HHS P30AG066506NIH HHS P50AG005146NIH HHS P50AG005681NIH HHS P50AG008702NIH HHS P50AG023501NIH HHS P50AG025688NIH HHS P50AG047366NIH HHS R56AG057195NIH HHS U01AG016976NIH HHS U01AG057195NIH HHS U24AG021886
Abstract
introductionOne goal of the Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is to investigate the genetic etiology of early onset (40-64 years) cognitive impairment. Toward this goal, LEADS participants are screened for known pathogenic variants.
methodsLEADS amyloid-positive early-onset Alzheimer's disease (EOAD) or negative early-onset non-AD (EOnonAD) cases were whole exome sequenced (N = 299). Pathogenic variant frequency in APP, PSEN1, PSEN2, GRN, MAPT, and C9ORF72 was assessed for EOAD and EOnonAD. Gene burden testing was performed in cases compared to similar-age cognitively normal controls in the Parkinson's Progression Markers Initiative (PPMI) study.
resultsPreviously reported pathogenic variants in the six genes were identified in 1.35% of EOAD (3/223) and 6.58% of EOnonAD (5/76). No genes showed enrichment for carriers of rare functional variants in LEADS cases. DISCUSSION: Results suggest that LEADS is enriched for novel genetic causative variants, as previously reported variants are not observed in most cases. HIGHLIGHTS: Sequencing identified eight cognitively impaired pathogenic variant carriers. Pathogenic variants were identified in PSEN1, GRN, MAPT, and C9ORF72. Rare variants were not enriched in APP, PSEN1/2, GRN, and MAPT. The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) is a key resource for early-onset Alzheimer's genetic research.
Indexed as
Alzheimer DiseaseAmyloid beta-Protein PrecursorC9orf72 ProteinGenetic TestingHumansLongitudinal StudiesMutationPresenilin-1Presenilin-2Amyloid beta-Protein PrecursorC9orf72 ProteinPresenilin-1Presenilin-2Alzheimer's diseaseAPPC9ORF7dementiaearly onsetgeneticsGRNMAPTPSEN1PSEN2sequencing
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