title: Association of prion protein with cognitive functioning in humans.
abstract: OBJECTIVE
  Recent animal studies have suggested a key role for cellular prion protein (PrPc) in the pathological consequences of amyloid plaque formation, the hallmark of Alzheimer's disease. This epidemiological study investigated whether serum concentrations of PrPc are associated with cognitive functioning in humans.
  
  
  METHODS
  Cross-sectional study of 1,322 participants from the elderly general population in Germany, aged 65+ years at baseline (2000-2002).
  
  
  METHODS
  Cognitive functioning was assessed by the COGTEL phone interview 5years after baseline. Serum PrPc was determined by a commercial immunoassay.
  
  
  RESULTS
  In multiple linear regression adjusted for important confounders, subjects in higher PrPc quintiles appeared to have lower cognitive functioning scores than those in the lowest PrPc quintile. Spline regression suggested pronounced non-linearity with an inverse association between PrPc and cognitive functioning levelling off beyond median PrPc. Cognitive subdomain-specific models produced somewhat heterogeneous results.
  
  
  CONCLUSIONS
  The findings are suggestive of an independent association of PrPc with cognitive functioning in humans. Confirmatory and longitudinal studies are needed to elucidate the potential of PrPc for applications in early risk stratification for cognitive impairment.
authors.affiliation: Division of Clinical Epidemiology and Aging Reseach, German Cancer Research Center, Heidelberg, Germany. lutzphilipp.breitling@med.uni-duesseldorf.de
authors.forename: Lutz Philipp
authors.initials: LP
authors.lastname: Breitling
authors.forename: Heiko
authors.initials: H
authors.lastname: Müller
authors.forename: Christa
authors.initials: C
authors.lastname: Stegmaier
authors.forename: Matthias
authors.initials: M
authors.lastname: Kliegel
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
mesh_terms: D000368:Aged; D000375:Aging / Q000523:psychology; D015415:Biomarkers / Q000097:blood; D003071:Cognition / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000097:blood / Q000453:epidemiology; D003430:Cross-Sectional Studies; D056344:Executive Function / Q000502:physiology; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011328:Prions / Q000097:blood / Q000502:physiology*
chemical_list: D015415:Biomarkers; D011328:Prions