Dataset Information

Characterizing Molecular and Synaptic Signatures in mouse models of Late-Onset Alzheimer's Disease Independent of Amyloid and Tau Pathology.

ABSTRACT:

Introduction

MODEL-AD is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to more accurately mimic LOAD than commonly used transgenic models.

Methods

We created the LOAD2 model by combining APOE4, Trem2*R47H, and humanized amyloid-beta. Mice aged up to 24 months were subjected to either a control diet or a high-fat/high-sugar diet (LOAD2+HFD) from two months of age. We assessed disease-relevant outcomes, including in vivo imaging, biomarkers, multi-omics, neuropathology, and behavior.

Results

By 18 months, LOAD2+HFD mice exhibited cortical neuron loss, elevated insoluble brain Aβ42, increased plasma NfL, and altered gene/protein expression related to lipid metabolism and synaptic function. In vivo imaging showed age-dependent reductions in brain region volume and neurovascular uncoupling. LOAD2+HFD mice also displayed deficits in acquiring touchscreen-based cognitive tasks.

Discussion

Collectively the comprehensive characterization of LOAD2+HFD mice reveal this model as important for preclinical studies that target features of LOAD independent of amyloid and tau.

SUBMITTER: Kotredes KP

PROVIDER: S-EPMC10769232 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Characterizing Molecular and Synaptic Signatures in mouse models of Late-Onset Alzheimer's Disease Independent of Amyloid and Tau Pathology.

Kotredes Kevin P KP Pandey Ravi S RS Persohn Scott S Elderidge Kierra K Burton Charles P CP Miner Ethan W EW Haynes Kathryn A KA Santos Diogo Francisco S DFS Williams Sean-Paul SP Heaton Nicholas N Ingraham Cynthia M CM Lloyd Christopher C Garceau Dylan D O'Rourke Rita R Herrick Sarah S Rangel-Barajas Claudia C Maharjan Surendra S Wang Nian N Sasner Michael M Lamb Bruce T BT Territo Paul R PR Sukoff Rizzo Stacey J SJ Carter Gregory W GW Howell Gareth R GR Oblak Adrian L AL

bioRxiv : the preprint server for biology 20231220

<h4>Introduction</h4>MODEL-AD is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to more accurately mimic LOAD than commonly used transgenic models.<h4>Methods</h4>We created the LOAD2 model by combining APOE4, Trem2*R47H, and humanized amyloid-beta. Mice aged up to 24 months were subjected to either a control diet or a high-fat/high-sugar diet (LOAD2+HFD) from two months of age. We assessed disease-relevant outcomes, including in vivo imagin ...[more]

PMID: 38187716

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Dataset Information

Characterizing Molecular and Synaptic Signatures in mouse models of Late-Onset Alzheimer's Disease Independent of Amyloid and Tau Pathology.

Introduction

Methods

Results

Discussion

Publications

Characterizing Molecular and Synaptic Signatures in mouse models of Late-Onset Alzheimer's Disease Independent of Amyloid and Tau Pathology.

Similar Datasets

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