NOS2 and early-onset autosomal dominant Alzheimer disease: Researches have also pointed out that T2DM-linked neurodegenerative disease (ND), such as Alzheimer’s disease (AD), is related to advanced glycosylation end product (AGE)-caused neuronal impairment via the inflammatory response, and metformin (1 mM) could rescue this inflammation-induced impairment through upregulating of ACC and inhibitory kappa B kinase (IKK), accompanied by restoring inducible nitric oxide synthase (iNOS) and cyclooxygenase-2(COX-2) in an AMPK-dependent way [67].