Fig. 5

NMDAR GluN3A deficiency induced sporadic AD. The graph shows age-dependent events and corresponding experimental evidence in the NMDAR GluN3A knockout mouse. A GluN3A deficiency caused by genetic mutation or functional dysfunction can result in slight but persistent neuronal hyperactivity and [Ca²⁺]_i elevations, subsequently leading to chronic inflammation, metabolism burden, and slowly evolved degenerative excitotoxicity. The synaptic impairment and programmed neuronal cell death in the hippocampus and cortex are correlated to progressive cognitive decline. Interestingly and important to note that significant endogenous Aβ plague formation in neurons and blood vessels occurs after, but not before, cognition decline and other functional deficits [127]