Abstract Objective Cell division cycle 42 (CDC42) regulates neurite outgrowth, neurotransmitter, and T help (Th) cell‐mediated neuroinflammation, while its clinical implication in Alzheimer's disease (AD) is not clear. The present study aimed to investigate the correlation of CDC42 with Th1, Th2, and Th17 cells, as well as CDC42’ longitudinal change and relation to cognitive function decline in AD patients. Methods 150 AD patients were enrolled, then their blood Th1, Th2, and Th17 cells were quantified by flow cytometry at baseline; CDC42 was detected by RT‐qPCR and MMSE score was assessed at baseline and during 3‐year follow‐up. Meanwhile, CDC42, Th1, Th2, and Th17 cells were quantified in 30 Parkinson's disease (PD) patients and 30 healthy controls (HCs). Results CDC42 (p 0.05). During a 3‐year follow‐up, CDC42 was gradually declined in AD patients (p