Glutamate Receptors in Alzheimer’s Disease: Mechanisms and Therapies

Abstract

Alzheimer’s disease (AD) manifests as a progressive loss in memory, cognition, and language that is commonly associated with elevated levels of amyloid-beta (Aβ) peptide and hyperphosphorylated tau in the brain. There is currently no cure for AD as its causes remain poorly understood. Accumulating evidence suggests that synaptic dysfunction is a major contributor early in disease pathogenesis prior to neuronal loss. Glutamatergic neurotransmission is particularly vulnerable to the neurotoxic effects of various assemblies of Aβ and hyperphosphorylated tau. Indeed, these toxic species act in synergy and severely disrupt excitatory synaptic transmission, synaptic plasticity, and network activity.