Unraveling the Role of TREM2 and CD33 in Alzheimer's Disease

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the accumulation of amyloid plaques and neurofibrillary tangles. This study investigates the role of two key genes, TREM2 and CD33, in AD pathogenesis. Gene expression profiles from human brain samples and transgenic mouse models were analyzed using data from the Gene Expression Omnibus. Differential gene expression analysis revealed significant upregulation of TREM2 and CD33 in AD samples compared to controls. Analysis of KEGG pathway, a database composed of biological pathway maps, showed TREM2 involvement in osteoclast differentiation and CD33 in hematopoietic cell lineage. String database analysis highlighted both genes' roles in regulating tumor necrosis factor production and cytokine production. Furthermore, TREM2 variants in AD patients were examined, identifying six variants (H157Y, R98W, D87N, T66M, Y38C, and Q33X) exclusive to AD samples. The R47H variant showed the strongest correlation with AD (p<0.001). The following SNPs of CD33 were identified as contributors to AD development: rs3826656, rs3865444, and rs12459419. These findings suggest that TREM2 and CD33 play crucial roles in AD progression, potentially through modulation of microglial function and inflammatory responses. These genes may serve as promising targets for developing novel AD therapeutics and biomarkers.