Evidence map›Paper›PMID 39670391›Full record

ArticlePacific Symposium on Biocomputing. Pacific Symposium on Biocomputing2025

Astrocyte Reactivity Polygenic Risk Score May Predict Cognitive Decline in Alzheimer's Disease.

Jared M Phillips, Julie A Schneider, David A Bennett, Paul K Crane, Shannon L Risacher, Andrew J Saykin, Logan C Dumitrescu, Timothy J Hohman, Alzheimer’s Disease Neuroimaging Initiative

Abstract read
In one paragraph

Article in Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing, 2025. 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.

No citing paper in PubMed yet.

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

9 authors.

Jared M PhillipsVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, 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.
Paul K CraneDepartment of Medicine, University of Washington, Seattle, WA, USA.
Shannon L RisacherIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Andrew J SaykinIndiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Logan C DumitrescuVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Timothy J HohmanVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA, timothy.j.hohman@vumc.org.
Alzheimer’s Disease Neuroimaging Initiative

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
MVP Data Integration into the ADSP Phenotype Harmonization ConsortiumU24AG074855 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CUCCARO, MICHAEL L, HOHMAN, TIMOTHY J · 2021 to 2025
$37.5M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Melissa Lamar · 2021 to 2026
$24.7M
Sex-Specific Genetic Drivers of Alzheimer's Disease EndophenotypesR01AG073439 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Logan C Dumitrescu · 2021 to 2026
$4.8M
Genetic Drivers of Resilience to Alzheimer's DiseaseR01AG059716 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI HOHMAN, TIMOTHY J · 2018 to 2022
$4.4M
AQP4 Associations with Alzheimer's Disease: A Multi-omics ApproachF31AG085980 · NIA · VANDERBILT UNIVERSITY · PI PHILLIPS, JARED · 2024 to 2024
$34k
NIA NIH HHS F31 AG085980NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG059716NIA NIH HHS R01 AG073439NIA NIH HHS U01 AG024904NIA NIH HHS U24 AG074855
6 · The paper itself

Abstract

Alzheimer's disease (AD) is a polygenic disorder with a prolonged prodromal phase, complicating early diagnosis. Recent research indicates that increased astrocyte reactivity is associated with a higher risk of pathogenic tau accumulation, particularly in amyloid-positive individuals. However, few clinical tools are available to predict which individuals are likely to exhibit elevated astrocyte activation and, consequently, be susceptible to hyperphosphorylated tau-induced neurodegeneration. Polygenic risk scores (PRS) aggregate the effects of multiple genetic loci to provide a single, continuous metric representing an individual's genetic risk for a specific phenotype. We hypothesized that an astrocyte activation PRS could aid in the early detection of faster clinical decline. Therefore, we constructed an astrocyte activation PRS and assessed its predictive value for cognitive decline and AD biomarkers (i.e., cerebrospinal fluid [CSF] levels of Aβ1-42, total tau, and p-tau181) in a cohort of 791 elderly individuals. The astrocyte activation PRS showed significant main effects on cross-sectional memory (β = -0.07, p = 0.03) and longitudinal executive function (β = -0.01, p = 0.03). Additionally, the PRS interacted with amyloid positivity (p.intx = 0.02), whereby indicating that amyloid burden modifies the association between the PRS and annual rate of language decline. Furthermore, the PRS was negatively associated with CSF Aβ1-42 levels (β = -3.4, p = 0.07) and interacted with amyloid status, such that amyloid burden modifies the association between the PRS and CSF phosphorylated tau levels (p.intx = 0.08). These findings suggest that an astrocyte activation PRS could be a valuable tool for early disease risk prediction, potentially enabling intervention during the interval between pathogenic amyloid and tau accumulation.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAstrocytesBiomarkersCognitive DysfunctionComputational BiologyMultifactorial Inheritancetau ProteinsAgedAged, 80 and overCohort StudiesFemaleGenetic Predisposition to DiseaseGenetic Risk ScoreHumansMaleAmyloid beta-Peptidesamyloid beta-protein (1-42)BiomarkersPeptide Fragmentstau Proteins

Identifiers

PMID39670391
PMCPMC11752824

What OpenQuestion holds

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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.