title: Plaque array method and proteomics-based identification of biomarkers from Alzheimer's disease serum.
abstract: BACKGROUND
  Progressive accumulation of amyloid plaques in the regions of brain, carotid and cerebral arteries is the leading cause of Alzheimer's disease (AD) and related dementia in affected patients. The early identification of individuals with AD remains a challenging task relying on symptomatic events and thus the development of a biomarker-based approach will significantly aid in the diagnosis of AD.
  
  
  METHODS
  Here we describe a flow cytometer-based serum biomarker identification method using plaque particles, and applying mass spectrometry based proteomic analysis of the isolated plaque particles for the identification of serum proteins present in the plaque particles.
  
  
  RESULTS
  We identified 195 serum proteins that participate in the process of plaque particle formation. Among the 195 proteins identified, 68.2% of them overlapped in abeta-42, cholesterol, tau-275 and α-synuclein plaque particles. Significantly, 22.5% of the proteins identified as bound to abeta-42 plaque particles generated in AD serum were unique when compared with cholesterol, α-synuclein and tau plaque particles. In age-matched control experiments, 15% of them showed in vitro insoluble abeta-42 particle formation and 59% of the identified plaque particle constituents from AD serum were also present in the insoluble plaque particles derived from control.
  
  
  CONCLUSIONS
  We have developed an in vitro method for plaque particle detection and identified serum protein markers that are associated with AD-related plaque particle formation. With further clinical validation, this assay may provide a novel, non-invasive means for the early detection of AD.
authors.affiliation: Plaxgen Inc., 428 Oakmead Parkway, Sunnyvale, CA 94085, United States. Electronic address: shan@plaxgen.com.
authors.forename: Shanmugavel
authors.initials: S
authors.lastname: Madasamy
authors.affiliation: Plaxgen Inc., 428 Oakmead Parkway, Sunnyvale, CA 94085, United States.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Chaudhuri
authors.affiliation: Amnis, Inc., 645 Elliott Avenue West, Suite 100, Seattle, WA 98119, United States.
authors.forename: Raymond
authors.initials: R
authors.lastname: Kong
authors.affiliation: Amnis, Inc., 645 Elliott Avenue West, Suite 100, Seattle, WA 98119, United States.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Alderete
authors.affiliation: Mass Spectrometry Facility, Mudd 125, 333 Campus Drive, Stanford University, Stanford, CA 94305, United States.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Adams
authors.affiliation: Stanford Shared FACS Facility, School of Medicine, Beckman Center, 279 Campus Drive, Stanford University, Stanford, CA 94305, United States.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Knaak
authors.affiliation: San Francisco General Hospital, 2M16 Clinical Chemistry, University of California, San Francisco, CA 94110, United States.
authors.forename: Weiming
authors.initials: W
authors.lastname: Ruan
authors.affiliation: San Francisco General Hospital, 2M16 Clinical Chemistry, University of California, San Francisco, CA 94110, United States.
authors.forename: Alan H B
authors.initials: AH
authors.lastname: Wu
authors.affiliation: Stanford Shared FACS Facility, School of Medicine, Beckman Center, 279 Campus Drive, Stanford University, Stanford, CA 94305, United States.
authors.forename: Marty
authors.initials: M
authors.lastname: Bigos
authors.affiliation: Molecular Medicine Research Institute, 428 Oakmead Parkway, Sunnyvale, CA 94085, United States.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Amento
mesh_terms: D000544:Alzheimer Disease / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D005434:Flow Cytometry; D006801:Humans; D013058:Mass Spectrometry; D058225:Plaque, Amyloid / Q000097:blood*; D040901:Proteomics
chemical_list: D015415:Biomarkers; D001798:Blood Proteins
keywords: Abeta-42; Alzheimer disease; Plaque; α-Synuclein