title: Quantification of the brain proteome in Alzheimer's disease using multiplexed mass spectrometry.
abstract: We have compared the brain proteome in the temporal neocortex between Alzheimer's disease (AD) patients and non-AD individuals by using shotgun mass spectrometry based on a stable isotope dimethyl labeling. A total of 827 unique proteins were identified and quantitated. Of these, 227 proteins were found in at least 9 out of 10 AD/control pairs and were further subjected to statistical analysis. A total of 69 proteins showed different levels (p-value < 0.05) in AD versus control brain samples. Of these proteins, 37 were increased and 32 were decreased as compared to the non-AD subjects. Twenty-three proteins comprise novel proteins that have not previously been reported as related to AD, e.g., neuronal-specific septin-3, septin-2, septin-5, dihydropteridine reductase, and clathrin heavy chain 1. The proteins with altered levels in the AD brain represent a wide variety of pathways suggested to be involved in the disease pathogenesis, including energy metabolism, glycolysis, oxidative stress, apoptosis, signal transduction, and synaptic functioning. Apart from leading to new insights into the molecular mechanisms in AD, the findings provide us with possible novel candidates for future diagnostic and prognostic disease markers.
authors.affiliation: Analytical Chemistry, Department of Chemistry-BMC and ‡Department Public Health/Geriatrics, Uppsala University , Uppsala, Sweden.
authors.forename: Sravani
authors.initials: S
authors.lastname: Musunuri
authors.forename: Magnus
authors.initials: M
authors.lastname: Wetterhall
authors.forename: Martin
authors.initials: M
authors.lastname: Ingelsson
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
authors.forename: Konstantin
authors.initials: K
authors.lastname: Artemenko
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergquist
authors.forename: Kim
authors.initials: K
authors.lastname: Kultima
authors.forename: Ganna
authors.initials: G
authors.lastname: Shevchenko
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001923:Brain Chemistry; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry / Q000145:classification; D020543:Proteome / Q000032:analysis* / Q000737:chemistry / Q000145:classification; D040901:Proteomics / Q000379:methods*
chemical_list: D009419:Nerve Tissue Proteins; D020543:Proteome