title: Roles of serum fibrinogen α chain-derived peptides in Alzheimer's disease.
abstract: OBJECTIVE
  To find a blood biomarker and disease-related peptides in Alzheimer's disease (AD), we comprehensively detected serum peptides.
  
  
  METHODS
  Ion intensity of serum peptides from 62 AD patients and 82 control subjects was measured by mass spectrometry.
  
  
  RESULTS
  A total of 157 peptides were detected from 30 AD patients and 30 healthy control (HC) subjects. Sixty out of the 157 peptide profiles discriminated between the AD and HC groups. Sixteen out of the 60 peptides were identified, 10 out of which were fragments of a fibrinogen α chain (FIBA). Among the 10 peptides, four and six peptides were derived from fibrinopeptide A (FPA, Aα1-16) and the C-terminal region of the αC-domain (αCDC, Aα557-610), respectively. The profile of 10 FIBA-derived peptides combined with age discriminated between the two groups with an area under the receiver operating characteristic curve (AUROC) of 0.940. Validation of this model using a testing set of 32 AD patients and 19 HC subjects showed an AUROC of 0.717, sensitivity of 65.6%, and specificity of 73.7% by a cutoff value of 0.56420. Another value, 0.04029, showed sensitivity of 96.9%, suggesting that subjects with values less than 0.04029 rarely possess AD. FPA and αCDC showed increased ion intensity in the AD group compared with the HC group (p < 0.05).
  
  
  CONCLUSIONS
  The profile of 10 FIBA-derived peptides combined with age would be a candidate biomarker for AD, which facilitates screening of the disease. The significant release of FPA and αCDC may be involved in the aberrant coagulation that leads to vascular damage in AD.
authors.affiliation: Department of Neuropsychiatry, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Noguchi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sato
authors.forename: Kouhei
authors.initials: K
authors.lastname: Nagai
authors.forename: Itaru
authors.initials: I
authors.lastname: Utagawa
authors.forename: Itsuku
authors.initials: I
authors.lastname: Suzuki
authors.forename: Mitsumi
authors.initials: M
authors.lastname: Arito
authors.forename: Nobuko
authors.initials: N
authors.lastname: Iizuka
authors.forename: Naoya
authors.initials: N
authors.lastname: Suematsu
authors.forename: Kazuki
authors.initials: K
authors.lastname: Okamoto
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kato
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Manae S
authors.initials: MS
authors.lastname: Kurokawa
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D005340:Fibrinogen / Q000032:analysis*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C464794:fibrinogen Aalpha; D005340:Fibrinogen
keywords: Alzheimer's disease; biomarker; fibrinogen α chain; mass spectrometry; peptidomics; serum samples