MAPT and Alzheimer disease: Interestingly, neuritic plaques, which have been associated with synaptic loss and cognitive decline in AD patients,58,59 are sites of Aβ–tau interaction58,60 and are thought to provide a microenvironment that facilitates the seeding and expansion of tau pathology and, hence, AD progression.61,62 In an amyloid context, A2AR neuronal dysregulation would therefore favour Aβ–tau interaction at neuritic plaques, the loss of synapses and, ultimately, the development of cognitive deficits.