title: Clinical and neurobiological correlates of soluble amyloid precursor proteins in the cerebrospinal fluid.
abstract: BACKGROUND
  According to a widely accepted hypothesis, the amyloid precursor protein (APP) is processed by two competing pathways: the amyloidogenic β-secretase-mediated pathway or the nonamyloidogenic α-secretase-mediated pathway. APP is cleaved preferentially through the nonamyloidogenic pathway in normal brain, whereas the balance shifts to the amyloidogenic pathway in Alzheimer's disease (AD). The levels of the α-secretase-cleaved soluble APP (sAPPα) and β-secretase-cleaved soluble APP (sAPPβ) in cerebrospinal fluid (CSF) are likely to reflect these competing mechanisms.
  
  
  METHODS
  We investigated the levels and the relationship between sAPPα and sAPPβ in the CSF of 64 patients with mild AD, 76 patients with mild cognitive impairment, and 12 cognitively healthy control subjects, as well as the effect of apolipoprotein E genotype and sex on soluble APP levels.
  
  
  RESULTS
  There was a significant positive correlation between sAPPα and sAPPβ levels in all three groups. sAPPα and sAPPβ concentrations were higher in patients with mild cognitive impairment compared with patients with AD. In the AD group, females exhibited higher sAPPα and sAPPβ levels than males. No influence of the apolipoprotein E genotype on soluble APP concentrations was detected.
  
  
  CONCLUSIONS
  The positive correlation between sAPPα and sAPPβ challenges the hypothesis that AD is caused by an imbalance of the α- and β-secretase APP proteolysis through competing mechanisms. Moreover, the differences in CSF levels of sAPPα and sAPPβ between male and female patients with AD may reflect a "sexual dimorphism" in the activity of the two APP processing pathways in AD.
authors: Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany. panos.alexopoulos@lrz.tu-muenchen.de
authors: Panagiotis
authors: P
authors: Alexopoulos
authors: Amalia
authors: A
authors: Tsolakidou
authors: Francesco
authors: F
authors: Roselli
authors: Anila
authors: A
authors: Arnold
authors: Timo
authors: T
authors: Grimmer
authors: Christine
authors: C
authors: Westerteicher
authors: Maria Rosaria
authors: MR
authors: Leante
authors: Hans
authors: H
authors: Förstl
authors: Paolo
authors: P
authors: Livrea
authors: Alexander
authors: A
authors: Kurz
authors: Robert
authors: R
authors: Perneczky
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases / Q000097:blood / Q000134:cerebrospinal fluid*; D001057:Apolipoproteins E / Q000235:genetics; D016009:Chi-Square Distribution; D060825:Cognitive Dysfunction / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012737:Sex Factors
chemical_list: D001057:Apolipoproteins E; D053829:Amyloid Precursor Protein Secretases