Evidence map›Paper›PMID 37780862›Full record

ArticleAlzheimer's & dementia (Amsterdam, Netherlands)

Early-onset Alzheimer's disease explained by polygenic risk of late-onset disease?

William G Mantyh, J Nicholas Cochran, Jared W Taylor, Iris J Broce, Ethan G Geier, Luke W Bonham, Ashlyn G Anderson, Daniel W Sirkis, Renaud La Joie, Leonardo Iaccarino and 12 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia (Amsterdam, Netherlands). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 14 citations in OpenAlex.

  1. RBFOX1 association with age at onset of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  2. Alzheimer's disease polygenic risk in early- and late-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Alzheimer's Disease Sequencing Project release 4 whole genome sequencing dataset.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  7. Blood biomarker profiles in young-onset neurocognitive disorders: A cohort study.The Australian and New Zealand journal of psychiatry · 2025
    Article
  8. Article
  9. Alzheimer's Disease Sequencing Project Release 4 Whole Genome Sequencing Dataset.medRxiv : the preprint server for health sciences · 2024
    Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 4 institutions in 1 country.

William G MantyhDepartment of Neurology University of Minnesota Minneapolis Minnesota USA.
J Nicholas CochranHudsonAlpha Institute for Biotechnology Huntsville Alabama USA.
Jared W TaylorHudsonAlpha Institute for Biotechnology Huntsville Alabama USA.
Iris J BroceMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Ethan G GeierMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Luke W BonhamMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Ashlyn G AndersonHudsonAlpha Institute for Biotechnology Huntsville Alabama USA.
Daniel W SirkisMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Renaud La JoieMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Leonardo IaccarinoMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Kiran ChaudharyMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Lauren EdwardsMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Amelia StromMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Harli GrantMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Isabel E AllenDepartment of Epidemiology and Biostatistics University of California San Francisco San Francisco California USA.
Zachary A MillerMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Marilu L Gorno-TempiniMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Joel H KramerMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Bruce L MillerMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Rahul S DesikanMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Gil D RabinoviciMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
Jennifer S YokoyamaMemory and Aging Center Department of Neurology University of California San Francisco San Francisco California USA.
University Memory and Aging Center · USUniversity of California, San Francisco · USHudsonAlpha Institute for Biotechnology · USUniversity of Minnesota · US

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Large Scale Genome SequencingU54HG003079 · NHGRI · WASHINGTON UNIVERSITY · PI DUTCHER, SUSAN K · 2004 to 2016
$445.7M
The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3M
Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI MONICA G. RIVERA-MINDT · 2016 to 2026
$226.7M
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
$119.8M
VCID and Stroke in a Bi-racial National CohortU01NS041588 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CUSHMAN, MARY, HOWARD, GEORGE · 2002 to 2022
$96.0M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
ARIC Neurocognitive Study (ARIC-NCS) Renewal 2023-2028U01HL096812 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI JOSEF CORESH, THOMAS H MOSLEY · 2010 to 2026
$65.7M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
THERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2M
VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GALASKO, DOUGLAS R · 1985 to 2018
$55.4M
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6 · The paper itself

Abstract

Early-onset Alzheimer's disease (AD) is highly heritable, yet only 10% of cases are associated with known pathogenic mutations. For early-onset AD patients without an identified autosomal dominant cause, we hypothesized that their early-onset disease reflects further enrichment of the common risk-conferring single nucleotide polymorphisms associated with late-onset AD. We applied a previously validated polygenic hazard score for late-onset AD to 193 consecutive patients diagnosed at our tertiary dementia referral center with symptomatic early-onset AD. For comparison, we included 179 participants with late-onset AD and 70 healthy controls. Polygenic hazard scores were similar in early- versus late-onset AD. The polygenic hazard score was not associated with age-of-onset or disease biomarkers within early-onset AD. Early-onset AD does not represent an extreme enrichment of the common single nucleotide polymorphisms associated with late-onset AD. Further exploration of novel genetic risk factors of this highly heritable disease is warranted.

Indexed as

age of onsetbiomarkersearly‐onset Alzheimer's diseaselate‐onset Alzheimer's diseasepolygenic risk

Identifiers

PMID37780862
PMCPMC10535074
OpenAlexW4387117195

What Socratic holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.