Fig 1. Possible mechanism of N-methyl-D-aspartate receptor and Aβ in Alzheimer Disease.

Deposition of amyloid plaques (Aβ) is characterized in Alzheimer’s disease (AD) which affects NMDAr resulting in Calcium-ion overload. High level of calcium-ion overload triggers critical events for neuronal dysfunction i.e. excitotoxicity, astrocyte activation and MMPs activation. Excitotoxic cell death (ECD) is an event due to increased intracellular Ca²⁺ by over-stimulation of NMDA receptor which results in synapse loss due to neurodegeneration. Aβ plays a role in inducing many alterations in glial cells by encouraging calcium-ion overload. The activated glial cells assemble around amyloid plaques or degenerating neurons and contribute in the neurodegenerative process in AD by causing neuroinflammation due to release of toxins or inflammatory mediators like cytokines. Astrocytes compete with the metabolic activity of neurons and neurotransmitters around synapses and considered as the major source of MMPs. MMPs are expressed in astrocytes and their activity is induced in the presence of Aβ. MMPs activation results in micro vascular inflammation as a consequent effect neuronal dysfunction due to BBB damage in AD.