Global quantitative analysis of the human brain proteome in Alzheimer’s and Parkinson’s Disease

• Type of Material: Article
• Authors: Lingyan Ping, Emory University; Duc M. Duong, Emory University; Luming Yin, Emory University; Marla Gearing, Emory University; James J Lah, Emory University; Allan I Levey, Emory University; Nicholas Seyfried, Emory University
• Language: English
• Date: 2018-03-13
• Publisher: Nature Publishing Group: Open Access Journals - Option C
• Publication Version: Final Published Version
• Copyright Statement: ©The Author(s) 2018.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/sdata.2018.36
• Title of Journal or Parent Work: Scientific Data
• ISSN: 2052-4463
• Volume: 5
• Start Page: 180036
• End Page: 180036
• Grant/Funding Information: N.T.S. is supported in part by an Alzheimer’s Association (ALZ), Alzheimer’s Research UK (ARUK), The Michael J. Fox Foundation for Parkinson’s Research (MJFF), and the Weston Brain Institute Biomarkers Across Neurodegenerative Diseases Grant (11060).; Funding was provided by the Accelerating Medicine Partnership AD grant U01AG046161, the NINDS Emory Neuroscience Core (P30NS055077), the National Institute on Aging (R01AG053960) and the Emory Alzheimer’s Disease Research Center (P50AG025688).
• Keywords: LEWY BODIES; Science & Technology; SHOTGUN PROTEOMICS; EXPRESSION; LABEL-FREE; RNA-SEQ DATA; ALPHA-SYNUCLEIN; Multidisciplinary Sciences; NEURODEGENERATIVE DISORDERS; MASS-SPECTROMETRY; Science & Technology - Other Topics; QUANTIFICATION; LTQ ORBITRAP
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Neuroscience; Health Sciences, Pathology

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-A nd 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.