Evidence mapPaperPMID 40964391Full record

ArticlebioRxiv : the preprint server for biology2025

Insulin resistance alters cortical inhibitory neurons and microglia to exacerbate Alzheimer's knock-in mouse phenotypes.

LaShae Nicholson, Si Jie Tang, Tejaswini Karra, Habiba Abouelatta, Stephen M Strittmatter

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In one paragraph

Article in bioRxiv : the preprint server for biology, 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

5 · Who and what money

Authors and funding

5 authors.

LaShae NicholsonDepartments of Neuroscience and Neurology, Yale School of Medicine, New Haven, CT, USA.
Si Jie TangDepartments of Neuroscience and Neurology, Yale School of Medicine, New Haven, CT, USA.
Tejaswini KarraDepartments of Neuroscience and Neurology, Yale School of Medicine, New Haven, CT, USA.
Habiba AbouelattaDepartments of Neuroscience and Neurology, Yale School of Medicine, New Haven, CT, USA.
Stephen M StrittmatterDepartments of Neuroscience and Neurology, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0001-8188-3092

Funding

Yale Alzheimer Disease Research CenterP30AG066508 · NIA · YALE UNIVERSITY · PI STEPHEN M STRITTMATTER, CHRISTOPHER H VAN DYCK · 2020 to 2026
$30.2M
Prion Protein in Alzheimer's Disease PathophysiologyR01AG034924 · NIA · YALE UNIVERSITY · PI STEPHEN M STRITTMATTER · 2010 to 2026
$9.6M
Synaptic selectivity for microglial-mediated damage in Alzheimer's DiseaseR01AG070926 · NIA · YALE UNIVERSITY · PI STRITTMATTER, STEPHEN M · 2024 to 2025
$1.6M
NIA NIH HHS P30 AG066508NIA NIH HHS R01 AG034924NIA NIH HHS R01 AG070926
6 · The paper itself

Abstract

Metabolic dysfunction contributes to the risk and progression of Alzheimer's disease (AD) through insulin signaling, but the cellular mechanisms are not fully understood. In this study, we examined the effects of streptozotocin-induced insulin deficiency or a high-fat, high-sugar (HFHS) diet-induced insulin resistance on cognitive function in knock-in AD mouse models expressing human mutant APP and wild-type tau. Both metabolic perturbations caused hyperglycemia, but only the HFHS diet resulted in weight gain and greater learning and memory deficits. The HFHS diet exacerbation occurred without changes in amyloid-β or phospho-tau accumulation and with only subtle alterations in microglial morphology. The basis for functional deficits was explored with single-nucleus transcriptomic analysis. Prominent gene expression changes in glial cells and cerebral cortex Layer 2 inhibitory neurons correlated with the enhanced behavioral deficits. In HFHS-fed AD mice, we observed a shared

Identifiers

PMID40964391
PMCPMC12439948

What Socratic 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 Socratic graph.