Evidence map›Paper›PMID 37333223›Full record

ArticlemedRxiv : the preprint server for health sciences2023

Cell-type-specific Alzheimer's disease polygenic risk scores are associated with distinct disease processes in Alzheimer's disease.

Hyun-Sik Yang, Ling Teng, Daniel Kang, Vilas Menon, Tian Ge, Hilary K Finucane, Aaron P Schultz, Michael Properzi, Hans-Ulrich Klein, Lori B Chibnik and 7 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 4 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 7 institutions in 1 country.

Hyun-Sik YangDepartment of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Ling TengDepartment of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Daniel KangDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Vilas MenonDepartment of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Tian GeHarvard Medical School, Boston, MA.
Hilary K FinucaneHarvard Medical School, Boston, MA.
Aaron P SchultzDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Michael ProperziDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Hans-Ulrich KleinDepartment of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Lori B ChibnikDepartment of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Julie A SchneiderRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Timothy J HohmanDepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Richard P MayeuxDepartment of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Keith A JohnsonDepartment of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Philip L De JagerDepartment of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Reisa A SperlingDepartment of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Broad Institute · USColumbia University Irving Medical Center · USBrigham and Women's Hospital · USMassachusetts General Hospital · USRush University Medical Center · USHarvard University · USVanderbilt University Medical Center · US

Funding

TRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2M
RECRUITMENT COREU19AG010483 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2013 to 2020
$80.6M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI SCHNEIDER, JULIE A. · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Open-Label Extension StudyR01AG063689 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI AISEN, PAUL S., SPERLING, REISA A. · 2019 to 2024
$30.8M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7M
Pathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6M
Immunogenetic contribution to the progression of preclinical Alzheimer's diseaseK23AG062750 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI YANG, HYUN-SIK · 2019 to 2023
$982k
NIA NIH HHS K23 AG062750NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG063689NIA NIH HHS U01 AG010483NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG061356NIA NIH HHS U19 AG010483
6 · The paper itself

Abstract

Alzheimer's disease (AD) heritability is enriched in glial genes, but how and when cell-type-specific genetic risk contributes to AD remains unclear. Here, we derive cell-type-specific AD polygenic risk scores (ADPRS) from two extensively characterized datasets. In an autopsy dataset spanning all stages of AD (n=1,457), astrocytic (Ast) ADPRS was associated with both diffuse and neuritic Aβ plaques, while microglial (Mic) ADPRS was associated with neuritic Aβ plaques, microglial activation, tau, and cognitive decline. Causal modeling analyses further clarified these relationships. In an independent neuroimaging dataset of cognitively unimpaired elderly (n=2,921), Ast-ADPRS were associated with Aβ, and Mic-ADPRS was associated with Aβ and tau, showing a consistent pattern with the autopsy dataset. Oligodendrocytic and excitatory neuronal ADPRSs were associated with tau, but only in the autopsy dataset including symptomatic AD cases. Together, our study provides human genetic evidence implicating multiple glial cell types in AD pathophysiology, starting from the preclinical stage.

Identifiers

PMID37333223
PMCPMC10274993
OpenAlexW4379380331

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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 OpenQuestion graph.