Characterizing molecular and synaptic signatures in mouse models of late-onset Alzheimer's disease independent of amyloid and tau pathology.

ABSTRACT:

Introduction

MODEL-AD (Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease) is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to capture the trajectory and progression of late-onset Alzheimer's disease (LOAD) more accurately.

Methods

We created the LOAD2 model by combining apolipoprotein E4 (APOE4), Trem2*R47H, and humanized amyloid-beta (Aβ). Mice were subjected to a control diet or a high-fat/high-sugar diet (LOAD2+HFD). We assessed disease-relevant outcome measures in plasma and brain including neuroinflammation, Aβ, neurodegeneration, neuroimaging, and multi-omics.

Results

By 18 months, LOAD2+HFD mice exhibited sex-specific neuron loss, elevated insoluble brain Aβ42, increased plasma n

SUBMITTER: Kotredes KP 

PROVIDER: S-EPMC11180851 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature