Association of prion protein with cognitive functioning in humans

ObjectivesRecent 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.Design, Setting, ParticipantsCross-sectional study of 1,322 participants from the elderly general population in Germany, aged 65 + years at baseline (2000–2002).MeasurementsCognitive functioning was assessed by the COGTEL phone interview 5 years after baseline. Serum PrPc was determined by a commercial immunoassay.ResultsIn 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.ConclusionThe 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.

► Recent studies suggest that PrPc plays a role in cognitive functioning.
► Data on human subjects are essentially lacking.
► Serum PrPc was measured in 1300 subjects with cognitive functioning data available.
► Higher PrPc levels tended to be associated with lower cognitive functioning scores.
► PrPc is a promising candidate marker of cognitive functioning and decline in humans.