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Age-dependent hippocampal proteomics in the APP/PS1 Alzheimer mouse model: a comparative analysis with classical SWATH/DIA and directDIA approaches

ABSTRACT: Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the human population, for which there is currently no cure. The cause of AD is unknown, however, the toxic effects of amyloid-β (Aβ) are believed to play a role in its onset. To investigate this, we examined changes in global protein levels in a hippocampal synaptosome fraction of the APP/PS1 mouse model of AD at 6 and 12 months of age (moa). Data independent acquisition (DIA), or SWATH, was used for a quantitative label-free proteomics analysis. We first assessed the usefulness of a recently improved directDIA workflow as alternative to conventional DIA data analysis using a project specific spectral library. Subsequently, we applied directDIA to the 6- and 12-moa APP/PS1 datasets and applied the Mass Spectrometry Downstream Analysis Pipeline (MS-DAP) for differential expression analysis and candidate discovery. We observed most regulation at 12-moa, in particular of proteins involved in Aβ homeostasis and microglial dependent synaptic pruning and/or immune response, such as APOE, CLU and C1QA-C

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: Sophie van der Spek

LAB HEAD: Ka Wan Li

PROVIDER: PXD025777 | Pride | 2021-06-24

REPOSITORIES: Pride

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