Figure 2: Postulated mechanism for the interaction between CHRNA7 polymorphisms, APOE ε4 and smoking.
From: CHRNA7 Polymorphisms and Dementia Risk: Interactions with Apolipoprotein ε4 and Cigarette Smoking
CHRNA7 encodes α7nAChR and may affect the pathogenesis of LOAD through the following mechanisms: (1) modulation of neurotransmitter release in presynaptic neurons38, (2) memory enhancement via mediating cholinergic neurotransmission5 and long-term potentiation6, and (3) neuroprotection via α7nAChR7. In APOE ε4 carriers, high levels of Aβ bind to α7nAChR, inactivating the receptor and decreasing its neuroprotective effect8. The nicotine in cigarette smoking is an agonist to α7nAChR which potentiates the neuroprotective effect of the receptor in preclinical studies11. Upregulation of α7nAChR was reported among smokers44. Abbreviations: nAChR, nicotinic acetylcholine receptor; APOE, apolipoprotein E; Aβ, amyloid β.
