@article{07f4f0f625dc412980c517478dfe7638,
title = "Quantitative measurement of intact alpha-synuclein proteoforms from post-mortem control and parkinson's disease brain tissue by intact protein mass spectrometry",
abstract = "A robust top down proteomics method is presented for profiling alpha-synuclein species from autopsied human frontal cortex brain tissue from Parkinson's cases and controls. The method was used to test the hypothesis that pathology associated brain tissue will have a different profile of post-translationally modified alpha-synuclein than the control samples. Validation of the sample processing steps, mass spectrometry based measurements, and data processing steps were performed. The intact protein quantitation method features extraction and integration of m/z data from each charge state of a detected alpha-synuclein species and fitting of the data to a simple linear model which accounts for concentration and charge state variability. The quantitation method was validated with serial dilutions of intact protein standards. Using the method on the human brain samples, several previously unreported modifications in alpha-synuclein were identified. Low levels of phosphorylated alpha synuclein were detected in brain tissue fractions enriched for Lewy body pathology and were marginally significant between PD cases and controls (p = 0.03).",
author = "Kellie, {John F.} and Higgs, {Richard E.} and Ryder, {John W.} and Anthony Major and Beach, {Thomas G.} and Adler, {Charles H.} and Kalpana Merchant and Knierman, {Michael D.}",
note = "Funding Information: The authors gratefully acknowledge the Michael J. Fox Foundation for partial financial support of this work. We are grateful to the Banner Sun Health Research Institute Brain and Body Donation Program of Sun City, Arizona for the provision of human brain tissue. The Brain and Body Donation Program is supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson{\textquoteright}s Disease and Related Disorders), the National Institute on Aging (P30 AG19610 Arizona Alzheimer{\textquoteright}s Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer{\textquoteright}s Research Center), and the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson{\textquoteright}s Disease Consortium). The authors also thank Dr. Jesus Gutierrez and Dr. Akihiko Kato for helpful discussion.",
year = "2014",
month = jul,
day = "23",
doi = "10.1038/srep05797",
language = "English (US)",
volume = "4",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}