Global quantitative analysis of the human brain proteome and phosphoproteome in Alzheimer’s disease

• Published in: Scientific data Vol. 7; no. 1; p. 315
• Main Authors: Ping, Lingyan, Kundinger, Sean R., Duong, Duc M., Yin, Luming, Gearing, Marla, Lah, James J., Levey, Allan I., Seyfried, Nicholas T.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.09.2020
• Subjects: 631/80/458/1733; 692/617/375/132/1283; Alzheimer Disease - metabolism; Brain - metabolism; Chromatography, Liquid; Data Descriptor; Humanities and Social Sciences; Humans; multidisciplinary; Phosphoproteins - metabolism; Proteome - analysis; Science; Science (multidisciplinary); Tandem Mass Spectrometry
• ISSN: 2052-4463; 2052-4463
• DOI: 10.1038/s41597-020-00650-8

Alzheimer’s disease (AD) is characterized by an early, asymptomatic phase (AsymAD) in which individuals exhibit amyloid-beta (Aβ) plaque accumulation in the absence of clinically detectable cognitive decline. Here we report an unbiased multiplex quantitative proteomic and phosphoproteomic analysis using tandem mass tag (TMT) isobaric labeling of human post-mortem cortex ( n  = 27) across pathology-free controls, AsymAD and symptomatic AD individuals. With off-line high-pH fractionation and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) on an Orbitrap Lumos mass spectrometer, we identified 11,378 protein groups across three TMT 11-plex batches. Immobilized metal affinity chromatography (IMAC) was used to enrich for phosphopeptides from the same TMT-labeled cases and 51,736 phosphopeptides were identified. Of these, 48,992 were quantified by TMT reporter ions representing 33,652 unique phosphosites. Two reference standards in each TMT 11-plex were included to assess intra- and inter-batch variance at the protein and peptide level. This comprehensive human brain proteome and phosphoproteome dataset will serve as a valuable resource for the identification of biochemical, cellular and signaling pathways altered during AD progression. Measurement(s) Proteomic Profile • Phosphoprotein Profile Technology Type(s) liquid chromatography-tandem mass spectrometry • immobilized metal affinity chromatography Factor Type(s) pathology-free control; asymptomatic AD; symptomatic AD • intra-batch variance • inter-batch variance Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.12901817