Identifying the molecular systems that influence cognitive resilience to Alzheimer's disease in genetically diverse mice.

Authors

Sarah E Heuer, The Jackson LaboratoryFollow
Sarah M Neuner, The Jackson LaboratoryFollow
Niran Hadad, The Jackson LaboratoryFollow
Kristen M S O'Connell, The Jackson LaboratoryFollow
Robert W Williams
Vivek M. Philip, The Jackson LaboratoryFollow
Chris Gaiteri
Catherine Kaczorowski, The Jackson LaboratoryFollow

Document Type

Article

Publication Date

9-1-2020

Keywords

JMG

JAX Source

Learn Mem 2020 Sep; 27(9):355-371

Volume

27

Issue

9

First Page

355

Last Page

371

ISSN

1549-5485

PMID

32817302

DOI

https://doi.org/10.1101/lm.051839.120

Grant

AG057914,AG050357,AG054180,AG062409

Abstract

Individual differences in cognitive decline during normal aging and Alzheimer's disease (AD) are common, but the molecular mechanisms underlying these distinct outcomes are not fully understood. We utilized a combination of genetic, molecular, and behavioral data from a mouse population designed to model human variation in cognitive outcomes to search for the molecular mechanisms behind this population-wide variation. Specifically, we used a systems genetics approach to relate gene expression to cognitive outcomes during AD and normal aging. Statistical causal-inference Bayesian modeling was used to model systematic genetic perturbations matched with cognitive data that identified astrocyte and microglia molecular networks as drivers of cognitive resilience to AD. Using genetic mapping, we identified

Comments

Open access under the terms of the Creative Commons Attribution License

Recommended Citation

Heuer S, Neuner S, Hadad N, O'Connell K, Williams R, Philip VM, Gaiteri C, Kaczorowski C. Identifying the molecular systems that influence cognitive resilience to Alzheimer's disease in genetically diverse mice. Learn Mem 2020 Sep; 27(9):355-371