Evidence map›Paper›PMID 42750154›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

Hippocampal snRNA-seq in Collaborative Cross reveals molecular signatures of cognitive resilience independent of chronological aging.

Yu Chen, Andrew R Ouellette, Yiding Cao, Jigang Zhang, Catherine C Kaczorowski

Abstract read
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In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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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

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5 · Who and what money

Authors and funding

5 authors.

Yu Chen *Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
Andrew R Ouellette *The Jackson Laboratory, Bar Harbor, Maine, USA.
Yiding CaoDepartment of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
Jigang ZhangThe Jackson Laboratory, Bar Harbor, Maine, USA.
Catherine C KaczorowskiDepartment of Neurology, University of Michigan, Ann Arbor, Michigan, USA.

Funding

Cell Type-Specific Proteins that Promote Resilience to Cognitive Aging and Alzheimer's Disease (Suppl)R01AG075818 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KACZOROWSKI, CATHERINE COOK · 2021 to 2025
$7.1M
Systems Genetics Analysis of Resilience to Alzheimers diseaseR01AG057914 · NIA · JACKSON LABORATORY · PI KACZOROWSKI, CATHERINE COOK · 2017 to 2021
$7.0M
Systems Control of Normal Aging and Alzheimer's DiseaseR01AG054180 · NIA · JACKSON LABORATORY · PI KACZOROWSKI, CATHERINE COOK · 2017 to 2021
$4.4M
Alzheimer's Association ZEN-21-846037Alzheimer's Association Research Fellowship AARF-24-1241640NIA NIH HHS R01 AG054180NIA NIH HHS R01AG054180NIA NIH HHS R01 AG057914NIA NIH HHS R01AG057914NIA NIH HHS R01 AG075818NIA NIH HHS R01AG075818
6 · The paper itself

Abstract

introductionGenetic factors contribute to variability in age-related cognitive decline, yet the molecular mechanisms underlying cognitive resilience remain poorly understood.

methodsWe performed single-nucleus RNA sequencing on hippocampal tissue from 107 genetically diverse Collaborative Cross mice across three ages (6, 12, and 18 months) and both sexes. Contextual fear memory was used as a continuous measure of cognitive function. Pseudobulk differential expression analyses identified transcriptional changes associated with aging and cognitive decline.

resultsAging and cognitive decline exhibited differential transcriptional signatures. Aging-related changes were modest and cell-type specific, with early responses in excitatory neurons followed by increased glial remodeling. Conversely, cognitive decline was associated with widespread transcriptional alterations predominantly in excitatory neurons, enriched for proteostasis and glutathione/redox pathways. DISCUSSION: These findings indicate that cognitive decline is not simply a consequence of aging but reflects distinct molecular processes in excitatory neurons. Proteostasis and redox pathways may represent conserved mechanisms supporting cognitive resilience.

Indexed as

AgingCognitionHippocampusRNA, Small NuclearAnimalsFearFemaleMaleMiceNeuronsProteostasisRNA, Small Nuclearcognitive resilienceCollaborative Crossdementiagenetically diverse mouse reference panelglutathione metabolismproteostasissnRNA‐seq

Identifiers

PMID42750154
PMCPMC13583060

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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.