title: Soluble amyloid precursor protein α and β in CSF in Alzheimer's disease.
abstract: OBJECTIVE
  Cerebral accumulation of amyloid β (Aβ) is a pathological hallmark of Alzheimer's disease (AD). Proteolytic processing of amyloid precursor protein (APP) by α- or β-secretase results in two soluble metabolites, sAPPα and sAPPβ, respectively. However, previous data have shown that both α- and β-secretase have multiple cleavage sites. The aim of this study was to characterize the C-termini of sAPPα and sAPPβ in cerebrospinal fluid (CSF) by mass spectrometry (MS) and to evaluate whether different combinations of these fragments better separate between AD patients and controls by comparing two different sAPP immunoassays.
  
  
  METHODS
  Using immunoprecipitation and high resolution MS, the APP species present in CSF were investigated. CSF levels of sAPPα and sAPPβ from patients with AD (n=43) and from non-demented controls (n=44) were measured using AlphaLISA and MSD immunoassays that employ different antibodies for C-terminal recognition of sAPPα.
  
  
  RESULTS
  Four different C-terminal forms of sAPP were identified, sAPPβ-M671, sAPPβ-Y681, sAPPα-Q686, and sAPPα-K687 (APP770 numbering). Neither immunoassay for the sAPP species could separate the two patient groups. The correlation (R(2)) between the two immunoassays was 0.41 for sAPPα and 0.45 for sAPPβ.
  
  
  CONCLUSIONS
  Using high resolution MS, we show here for the first time that sAPPα in CSF ends at Q686 and K687. The findings also support the conclusion from several previous studies that sAPPα and sAPPβ levels are unaltered in AD.
authors.affiliation: Department of Psychiatry and Neurochemistry, Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden. gunnar.brinkmalm@neuro.gu.se
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brinkmalm
authors.forename: Ann
authors.initials: A
authors.lastname: Brinkmalm
authors.forename: Philippe
authors.initials: P
authors.lastname: Bourgeois
authors.forename: Rita
authors.initials: R
authors.lastname: Persson
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
authors.forename: Erik
authors.initials: E
authors.lastname: Portelius
authors.forename: Marc
authors.initials: M
authors.lastname: Mercken
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
authors.forename: Stéphane
authors.initials: S
authors.lastname: Parent
authors.forename: Francesco
authors.initials: F
authors.lastname: Lipari
authors.forename: Annika
authors.initials: A
authors.lastname: Ohrfelt
authors.forename: Maria
authors.initials: M
authors.lastname: Bjerke
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Magdalena
authors.initials: M
authors.lastname: Nutu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid*; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D053719:Tandem Mass Spectrometry; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins