Abstract
Patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD) often have overlap in clinical presentation and brain neuropathology suggesting that these two diseases share common underlying mechanisms. Currently, the molecular pathways linking AD and PD are incompletely understood. Utilizing Tandem Mass Tag (TMT) isobaric labeling and synchronous precursor selection-based MS3 (SPS-MS3) mass spectrometry, we performed an unbiased quantitative proteomic analysis of post-mortem human brain tissues (n=80) from four different groups defined as controls, AD, PD, and co-morbid AD/PD cases across two brain regions (frontal cortex and anterior cingulate gyrus). In total, we identified 11 840 protein groups representing 10 230 gene symbols, which map to ~65% of the protein coding genes in brain. The utility of including two reference standards in each TMT 10-plex assay to assess intra- and inter-batch variance is also described. Ultimately, this comprehensive human brain proteomic dataset serves as a valuable resource for various research endeavors including, but not limited to, the identification of disease-specific protein signatures and molecular pathways that are common in AD and PD.
Highlights
Background & SummaryMany neurodegenerative diseases are found to have common cellular and molecular mechanisms such as pathological protein aggregation and have been collectively termed as ‘proteinopathies’[1,2]
We report a large-scale quantitative proteomic dataset of Alzheimer’s disease (AD) and Parkinson’s disease (PD) postmortem brain tissue that can be used to further our understanding of these related neurodegenerative diseases
We identified 127 321 total unique peptides from over 1.5 million peptide spectral matches (PSMs), which mapped to 11 840 unique proteins groups
Summary
Background & SummaryMany neurodegenerative diseases are found to have common cellular and molecular mechanisms such as pathological protein aggregation and have been collectively termed as ‘proteinopathies’[1,2]. We applied TMT labeling with SPS-MS3 to achieve comprehensive global quantitation of two brain regions (frontal cortex and anterior cingulate gyrus) from four different groups: healthy controls, AD, PD, and co-morbid AD/PD cases.
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