Prion protein (PrPc) promotes beta-amyloid plaque formation
- PMID: 15917101
- DOI: 10.1016/j.neurobiolaging.2004.10.004
Prion protein (PrPc) promotes beta-amyloid plaque formation
Abstract
Prion protein (PrP) has been localized to amyloid-beta (Abeta) senile plaques in aging and Alzheimer disease, but it is unknown whether PrP is directly involved in plaque formation or represents a reaction to amyloid deposition. To evaluate possible functional effects of PrP in Abeta plaque formation, we analyzed bigenic mice (TgCRND8/Tg7), carrying mutant human amyloid precursor protein (APP) 695 (APP(Swed+Ind), TgCRND8) as well as the wild-type Syrian hamster prion protein gene (sHaPrP, Tg7), showing Abeta plaques at 3 months of age as well as highly increased HaPrP(c) levels. Compared to the control group, consisting of animals carrying only mutant APP, bigenic mice showed a higher number of senile plaques in the cerebral cortex, while APP transcription and Abeta40/Abeta42 levels were unchanged. Double-labelling immunofluorescence showed co-localization of Abeta and PrP in virtually all plaques in the brains of both control and experimental animals. Our data suggest that PrP promotes plaque formation, and that this hitherto unknown functional role of PrP appears to be mediated by increased Abeta aggregation rather than by altered APP transcription or processing.
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