Mouse model of Alzheimer's disease demonstrates differential effects of early disease pathology on various brain regions

Liting Deng; Vivek K Gupta; Yunqi Wu; Kanishka Pushpitha; Nitin Chitranshi; Veer B Gupta; Matthew J Fitzhenry; Masoud Zabet Moghaddam; Tim Karl; Ghasem Hosseini Salekdeh; Stuart L Graham; Paul A Haynes; Mehdi Mirzaei

doi:10.1002/pmic.202000213

Mouse model of Alzheimer's disease demonstrates differential effects of early disease pathology on various brain regions

Proteomics. 2021 Apr;21(7-8):e2000213. doi: 10.1002/pmic.202000213. Epub 2021 Mar 9.

Affiliations

¹ Department of Molecular Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, New South Wales, Australia.
² Faculty of Medicine and Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
³ School of Medicine, Deakin University, Geelong, Victoria, Australia.
⁴ Australian Proteome Analysis Facility (APAF), Macquarie University, Sydney, New South Wales, Australia.
⁵ Center for Biotechnology and Genomics, Texas Tech University, Lubbock, Texas, USA.
⁶ School of Medicine, Western Sydney University, Penrith, New South Wales, Australia.

PMID: 33559908
DOI: 10.1002/pmic.202000213

Abstract

Different parts of the brain are affected distinctively in various stages of the Alzheimer's disease (AD) pathogenesis. Identifying the biochemical changes in specific brain regions is key to comprehend the neuropathological mechanisms in early pre-symptomatic phases of AD. Quantitative proteomics profiling of four distinct areas of the brain of young APP/PS1 mouse model of AD was performed followed by biochemical pathway enrichment analysis. Findings revealed fundamental compositional and functional shifts even in the early stages of the disease. This novel study highlights unique proteome and biochemical pathway alterations in specific regions of the brain that underlie the early stages of AD pathology and will provide a framework for future longitudinal studies. The proteomics data were deposited into the ProteomeXchange Consortium via PRIDE with the identifier PXD019192.

Keywords: APP/PS1; Alzheimer's disease; amyloid beta; cerebellum; cortex; hippocampus; proteomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / genetics
Alzheimer Disease / metabolism*
Alzheimer Disease / pathology
Amyloid beta-Protein Precursor / genetics
Animals
Brain / metabolism*
Brain / pathology
Disease Models, Animal
Mice
Presenilin-1 / genetics
Proteome / metabolism*

Substances

Amyloid beta-Protein Precursor
Presenilin-1
Proteome