Behavioral, metabolic, and lipidomic characterization of the 5xFADxTg30 mouse model of Alzheimer's disease

J P S Marshall; K Huynh; G I Lancaster; J Ng; J M Collins; G Pernes; A Liang; T Featherby; N A Mellet; B G Drew; A C Calkin; A E King; P J Meikle; M A Febbraio; P A Adlard; D C Henstridge

doi:10.1016/j.isci.2024.108800

Behavioral, metabolic, and lipidomic characterization of the 5xFADxTg30 mouse model of Alzheimer's disease

iScience. 2024 Jan 4;27(2):108800. doi: 10.1016/j.isci.2024.108800. eCollection 2024 Feb 16.

Authors

J P S Marshall^{1

2

3}, K Huynh^{1

4

5}, G I Lancaster^{1

6}, J Ng⁷, J M Collins⁸, G Pernes¹, A Liang¹, T Featherby³, N A Mellet¹, B G Drew^{1

4

9}, A C Calkin^{1

4

9}, A E King⁸, P J Meikle^{1

4

5}, M A Febbraio¹⁰, P A Adlard³, D C Henstridge^{1

7}

Affiliations

¹ Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
² School of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia.
³ The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
⁴ Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, VIC, Australia.
⁵ Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Bundoora, VIC, Australia.
⁶ Department of Immunology, Monash University, Melbourne, VIC, Australia.
⁷ School of Health Sciences, The University of Tasmania, Launceston, TAS, Australia.
⁸ Wicking Dementia Research and Education Centre, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia.
⁹ Central Clinical School, Monash University, Melbourne, VIC, Australia.
¹⁰ Monash Institute of Pharmaceutical Sciences, Melbourne, VIC, Australia.

Abstract

Alzheimer's disease (AD) is associated with both extracellular amyloid-β (Aβ) plaques and intracellular tau-containing neurofibrillary tangles (NFT). We characterized the behavioral, metabolic and lipidomic phenotype of the 5xFADxTg30 mouse model which contains overexpression of both Aβ and tau. Our results independently reproduce several phenotypic traits described previously for this model, while providing additional characterization. This model develops many aspects associated with AD including frailty, decreased survival, initiation of aspects of cognitive decline and alterations to specific lipid classes and molecular lipid species in the plasma and brain. Notably, some sex-specific differences exist in this model and motor impairment with aging in this model does compromise the utility of the model for some movement-based behavioral assessments of cognitive function. These findings provide a reference for individuals interested in using this model to understand the pathology associated with elevated Aβ and tau or for testing potential therapeutics for the treatment of AD.

Keywords: Animal physiology; Behavioral neuroscience; Lipidomics; Neuroscience.