Indexed on: 01 May '13Published on: 01 May '13Published in: Intractable & rare diseases research
Alzheimer's disease (AD) is a devastating neurodegenerative disease with progressive loss of memory and cognitive function, pathologically hallmarked by aggregates of the amyloid-beta (Aβ) peptide and hyperphosphorylated tau in the brain. Aggregation of Aβ under the form of amyloid fibrils has long been considered central to the pathogenesis of AD. However, recent evidence has indicated that soluble Aβ oligomers, rather than insoluble fibrils, are the main neurotoxic species in AD. The cellular prion protein (PrP(C)) has newly been identified as a cell surface receptor for Aβ oligomers. PrP(C) is a cell surface glycoprotein that plays a key role in the propagation of prions, proteinaceous infectious agents that replicate by imposing their abnormal conformation to PrP(C) molecules. In AD, PrP(C) acts to transduce the neurotoxic signals arising from Aβ oligomers, leading to synaptic failure and cognitive impairment. Interestingly, accumulating evidence has also shown that aggregated Aβ or tau possesses prion-like activity, a property that would allow them to spread throughout the brain. In this article, we review recent findings regarding the function of PrP(C) and its role in AD, and discuss potential therapeutic implications of PrP(C)-based approaches in the treatment of AD.