Proteomics of neurodegenerative diseases: analysis of human post-mortem brain

Abstract

Dementias are prevalent brain disorders in the aged population. Dementias pose major socio-medical burden, but currently there is no cure available. Novel proteomics approaches hold promise to identify alterations of the brain proteome that could provide clues on disease etiology, and identify candidate proteins to develop further as a biomarker. In this review, we focus on recent proteomics findings from brains affected with Alzheimer's Disease, Parkinson Disease Dementia, Frontotemporal Dementia, and Amyotrophic Lateral Sclerosis. These studies confirmed known cellular changes, and in addition identified novel proteins that may underlie distinct aspects of the diseases. This article is part of the special issue "Proteomics".

Keywords: Alzheimer's disease; brain; dementia; mass spectrometer; neuroproteomics.

Figure 1

Quantitative neuroproteomics workflow. From left to right panels are the schematic representations of sample selection from Alzheimer's disease brains or heathy controls, the collection of brain areas by laser microdissection (LMD; upper panel) or manual dissection (lower panel), sample preparation for the downstream analysis by data dependent acquisition (upper panel) or isobaric multiplex labeling strategies for relative quantitative proteomics (lower panel), and the actual measurements of the peptides by LC‐MS/MS and the subsequent data analysis.