Global quantitative analysis of the human brain proteome in Alzheimer’s and Parkinson’s Disease
Open accessAbstract
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.
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In our unbiased network analysis of >8000 proteins from AD DLPFC, we resolved an ECM-associated module with highly significant endothelial enrichment and relatively weak glial co-expression.
“Among the resulting 44 modules, we resolved an ECM-associated module with highly significant endothelial enrichment and relatively weak glial co-expression.”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [75]
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References 65 · Cited by 221
- Authors
- Ping, L., Duong, D. M., Yin, L., Gearing, M., Lah, J. J., Levey, A. I., & Seyfried, N. T.
- Affiliations
- Emory University (US)
- Corresponding author
- Seyfried, Nicholas T.
- Venue
- Scientific Data
- Published
- 2018-03-13
- Volume
- 5
- Issue
- 1
- Pages
- 180036-180036
- ISSN
- 2052-4463 (ISSN-L)
- PMC
- PMC5848788
- OpenAlex
- W2791403874
- Cited by
- 221
- References
- 65
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 25 · 2023: 26 · 2022: 32 · 2021: 40 · 2020: 31 · 2019: 24 · 2018: 9
- Type
- data paper
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Data (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Michael J. Fox Foundation for Parkinson's Research (11060)
- Alzheimer's Association (11060)
- Emory University (R01AG053960, P50AG025688, P30NS055077)
- Weston Brain Institute (11060)
- Alzheimer's Disease Research Center, Emory University (P50 AG025688)
- National Institute on Aging (U01AG046161, RF1AG057471, P50AG025688, R01AG053960)
- National Institute of Neurological Disorders and Stroke (P30NS055077)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, Parkinson's disease, brain proteome, postmortem brain, frontal cortex, anterior cingulate cortex, reference materials, quantitative proteomics
- MeSH terms
- Alzheimer Disease, Brain, Humans, Parkinson Disease, Mass Spectrometry, Comorbidity, Proteome, Proteomics
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