P2Y receptors in Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of dementia, affecting more than 10% of people over the age of 65. Age is the greatest risk factor for AD, although a combination of genetic, lifestyle and environmental factors also contribute to disease development. Common features of AD are the formation of plaques composed of beta-amyloid peptides (A) and neuronal death in brain regions involved in learning and memory. Although A is neurotoxic, the primary mechanisms by which A affects AD development remain uncertain and controversial. Mouse models overexpressing amyloid precursor protein and A have revealed that A has potent effects on neuroinflammation and cerebral blood flow that contribute to AD progression. Therefore, it is important to consider how endogenous signalling in the brain responds to A and contributes to AD pathology. In recent years, A has been shown to affect ATP release from brain and blood cells and alter the expression of G protein-coupled P2Y receptors that respond to ATP and other nucleotides. Accumulating evidence reveals a prominent role for P2Y receptors in AD pathology, including A production and elimination, neuroinflammation, neuronal function and cerebral blood flow.