Detecting the Effect of Genetic Diversity on Brain Composition in an Alzheimer's Disease Mouse Model

Overview

Journal bioRxiv

Date 2023 Mar 13

PMID 36909528

Authors

Brianna Gurdon

Sharon C Yates

Gergely Csucs

Nicolaas E Groeneboom

Niran Hadad

Maria Telpoukhovskaia

Andrew Ouellette

Tionna Ouellette

Kristen OConnell

Surjeet Singh

Tom Murdy

Erin Merchant

Ingvild Bjerke

Heidi Kleven

Ulrike Schlegel

Trygve B Leergaard

Maja A Puchades

Jan G Bjaalie

Catherine C Kaczorowski

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD) is characterized by neurodegeneration, pathology accumulation, and progressive cognitive decline. There is significant variation in age at onset and severity of symptoms highlighting the importance of genetic diversity in the study of AD. To address this, we analyzed cell and pathology composition of 6- and 14-month-old AD-BXD mouse brains using the semi-automated workflow (QUINT); which we expanded to allow for nonlinear refinement of brain atlas-registration, and quality control assessment of atlas-registration and brain section integrity. Near global age-related increases in microglia, astrocyte, and amyloid-beta accumulation were measured, while regional variation in neuron load existed among strains. Furthermore, hippocampal immunohistochemistry analyses were combined with bulk RNA-sequencing results to demonstrate the relationship between cell composition and gene expression. Overall, the additional functionality of the QUINT workflow delivers a highly effective method for registering and quantifying cell and pathology changes in diverse disease models.

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