Brain proteome analysis of APPswe mouse model at the early stages of Alzheimer's disease pathology

ABSTRACT: Plaques consisting of amyloid-β (Aβ) in the brain are characteristic for patients with Alzheimer´s disease. Aβ is enzymatically generated of the amyloid precursor protein (APP). During the disease, Aβ starts to aggregate forming soluble oligomers, soluble protofibrils and eventually insoluble fibrils. Aβ pathology starts mainly at the hippocampus and the surrounding cortical area. Mice overexpressing the A�-precursor protein with the Swedish mutation (APPswe) are one of the most commonly used animal models in Alzheimer’s field. These mice overexpress APP with the Swedish mutation (KM670/671NL), which is adjacent to the β-secretase cleavage site on APP. This results in increased production of Aβ. The aim of this study was to study the proteome of APPswe brain at the early stages (7-8 months old) of the disease, before plaque onset, which starts at around 11-12 months of age in this mouse model. Homogenates of the hippocampus and the rest of the cerebrum from 7-8 months-old APPswe and wild-type (WT) controls were lysed. Afterwards, filter aided tryptic digestion was performed. The resulting peptides were analyzed using LC-UDMSE. The data was searched against a randomized mouse database and label-free quantification analysis was done. In total 2487 proteins were found. In the hippocampus of APPswe mice, the levels of 1283 proteins were significantly altered compared to WT controls. While 1379 proteins were significantly altered in the rest of the cerebrum of APPswe mice compared to WT controls. Among these, mitochondrial proteins and proteins involved in neuron's development were significantly downregulated, suggesting mitochondrial dysfunction and dysregulation of neuron’s growth in the brain of APPswe mice at already this stage of the disease.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Erik Jansson  

LAB HEAD: Erik Jansson

PROVIDER: PXD026566 | Pride | 2021-06-28

REPOSITORIES: Pride