title: Plasma protein profiling for potential biomarkers in the early diagnosis of Alzheimer's disease.
abstract: OBJECTIVE
  Alzheimer's disease (AD) is the most common cause of dementia in elderly persons. Since the pathology of AD develops slowly from a preclinical or early phase into a fully expressed clinical syndrome, at the time of diagnosis the disease has been progressing for many years. To facilitate the early diagnosis of AD, we performed protein profiling of blood in patients with mild AD as defined by the Functional Assessment Staging (FAST) scale.
  
  
  METHODS
  Plasma samples from mild AD patients and healthy controls were analyzed using two-dimensional differential gel electrophoresis (2D-DIGE) combined with matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF/MS) followed by peptide mass fingerprinting.
  
  
  RESULTS
  Three downregulated proteins were identified: apolipoprotein A-1, alpha-2-HS-glycoprotein, and afamin. Two proteins, including apolipoprotein A-4 and fibrinogen gamma chain, were upregulated in mild AD patients.
  
  
  CONCLUSIONS
  Our results suggest that altered expression levels of these proteins in plasma may yield candidate biomarkers for the early diagnosis of AD.
  
  
  BACKGROUND
  AD, Alzheimer's disease; FAST, Functional Assessment Staging; 2D-DIGE, two-dimensional differential gel electrophoresis; MALDI-TOF/TOF/MS, matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry; CSF, cerebrospinal fluid; Aβ, amyloid beta; MMSE, Mini Mental State Examination; MRI, magnetic resonance imaging; NINCDS-ADRDA, National Institute for Neurological Diseases and Stroke/Alzheimer's Disease and Related Disorders Association; CHAPS, 3-((3-cholamidopropyl) dimethylammonio)-1-propanesulfonate; DTT, dithiothreitol; SDS-PAGE, SDS-polyacrylamide gel electrophoresis; DIA, differential in-gel analysis; BVA, biological variation analysis; CBB, Coomassie brilliant blue; 2DE, two-dimensional gel electrophoresis; TFA, trifluoroacetic acid; ACTH, adrenocorticotropic hormone; Apo A-1, apolipoprotein A-1; AHSG, alpha-2-HS-glycoprotein; Apo A-4, apolipoprotein A-4; MCI, mild cognitive impairment.
authors.affiliation: a Department of Environmental and Molecular Medicine , Mie University Graduate School of Medicine , Tsu , Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kitamura
authors.affiliation: a Department of Environmental and Molecular Medicine , Mie University Graduate School of Medicine , Tsu , Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Usami
authors.affiliation: b Graduate School of Regional Innovation Studies , Mie University , Tsu , Japan.
authors.forename: Sahoko
authors.initials: S
authors.lastname: Ichihara
authors.affiliation: c Department of Dementia Prevention and Therapeutics , Mie University Graduate School of Medicine , Tsu , Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kida
authors.affiliation: c Department of Dementia Prevention and Therapeutics , Mie University Graduate School of Medicine , Tsu , Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Satoh
authors.affiliation: c Department of Dementia Prevention and Therapeutics , Mie University Graduate School of Medicine , Tsu , Japan.|d Department of Neurology , Mie University Graduate School of Medicine , Tsu , Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tomimoto
authors.affiliation: a Department of Environmental and Molecular Medicine , Mie University Graduate School of Medicine , Tsu , Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Murata
authors.affiliation: a Department of Environmental and Molecular Medicine , Mie University Graduate School of Medicine , Tsu , Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Oikawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D016632:Apolipoprotein A-I / Q000097:blood*; D001054:Apolipoproteins A / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D002352:Carrier Proteins / Q000097:blood*; D042241:Early Diagnosis; D005260:Female; D005340:Fibrinogen; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D040901:Proteomics; D012709:Serum Albumin; D000075462:Serum Albumin, Human; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D057825:Two-Dimensional Difference Gel Electrophoresis; D060749:alpha-2-HS-Glycoprotein / Q000032:analysis*
chemical_list: C088246:AFM protein, human; C556354:AHSG protein, human; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D015415:Biomarkers; D001798:Blood Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; C427756:P2-C protein, fibrinogen; D010446:Peptide Fragments; D012709:Serum Albumin; D060749:alpha-2-HS-Glycoprotein; C022205:apolipoprotein A-IV; D005340:Fibrinogen; D000075462:Serum Albumin, Human
keywords: 2D-DIGE; Alzheimer’s disease; biomarkers; plasma; proteomics