Figure 1.

Dysfunction of neurotransmission in AD. Accumulation of Aβ plaques and NFT in AD cause impairment of the circadian rhythm, cognition, learning, memory, motor function, mood, sleep and stress response. These pathologies are toxic to neurotransmission systems, affecting cholinergic, glutamatergic, serotonergic and dopaminergic systems. Amyloid-beta plaques and NFT can inhibit the release of ACh and choline acetyltransferase, an enzyme that regulates ACh synthesis, which reinforces the inhibition effect of ACh. Amyloid-beta plaques and NFT can cause mitochondrial damage in glutamatergic neurons. The mitochondrial damage leads to inflammation due to excessive influx of Ca²⁺ and excessive efflux of Mg²⁺ that affect the activation of glutamatergic neurons and decreases the activation of NMDA receptor. The excessive influx of Ca²⁺ in glutamatergic neurons leads to inhibition of choline acetyltransferase and further inhibits the synthesis of ACh. However, the detailed mechanisms are not yet understood, as some studies showed the upregulation of GABA in certain regions but downregulation of GABA in other regions. Amyloid-beta plaques also disrupt the homeostatsis of serotonin (5-HT) by inhibiting the binding of serotonin receptor (5-HT2A) and disrupting the dopaminergic system. Abbreviations: Aβ, Amyloid-beta; NFT, neurofibrillary tangle.