Alzheimer disease neocortex LC-MSMS

ABSTRACT: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is pathologically characterized by amyloid β-peptide (Aβ)-containing plaques and the generation of neurofibrillary tangles (NFTs). Although proteome profile changes have been reported in AD brains, it is unclear whether they represent a continuous process from mild to severe changes or whether there is a sequence, with step-by-step involvement of proteins. To address this we analyzed neocortex samples of 19 control cases without signs of neurodegeneration (nonAD), 17 pathologically-diagnosed preclinical AD (p-preAD), and 17 symptomatic AD cases by mass spectrometry after homogenization and separation into soluble, dispersible, membrane-associated, and plaque-associated fractions. Here, we show three classes of proteins exhibiting changed levels during the pathogenesis and progression of AD from the AD pathology-free to the symptomatic stage: five early- and 24 late-responding proteins and 17 gradually changing proteins. The identified proteins and hierarchy point to endocytosis/synaptic vesicle cycle-related processes as key elements in the initiation of AD pathology in the neocortex, while later changes document the resulting neurodegenerative process.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Xiaohang Li  

LAB HEAD: Dietmar Rudolf Thal

PROVIDER: PXD020020 | Pride | 2021-06-21

REPOSITORIES: Pride