Coupling relationship between glucose and oxygen metabolisms to serve as an imaging biomarker for Alzheimer's disease.

CD33 rs3865444 polymorphism is closely associated with the risk of Alzheimer's disease (AD), and CD33 is part of the sialic acid-binding Ig-superfamily of lectins (SIGLECs). Immunostaining experiments in previous studies have confirmed the expression of CD33 in human brain microglial cells, and an increase in CD33 mRNA expression in the brain microglial cells of patients with cognitive impairment has been observed. The minor allele CD33 rs3865444 (A) has a protective effect against Alzheimer's disease pathology and is associated with reduced CD33 expression and clearance of amyloid-beta plaques. The risk allele CD33 rs3865444 (C) can cause abnormal activation of microglial cells, thereby inducing neuroinflammation, accompanied by an increase in metabolic levels. We hypothesize that the CD33 rs3865444 polymorphism may affect the coupling between glucose metabolism and neuronal activity, thereby influencing individual cognitive trajectories and the progression of cognitive impairment. In this study, we included 107 patients with mild cognitive impairment, among whom the limbic-orbital frontal cortex glucose-oxygen coupling (G/O) coefficient of the CD33 rs3865444 CC group was significantly reduced. Additionally, the results of the mediation analysis showed that the glucose-oxygen coupling coefficient completely mediated the effect of the CD33 rs3865444 polymorphism on the rate of clinical dementia rating increase.