Relation of CDC42, Th1, Th2, and Th17 cells with cognitive function decline in Alzheimer's disease

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 < 0.001) and Th2 cells (p < 0.001) were lowest in AD patients, followed by PD patients, highest in HCs; but Th1 cells (p = 0.001) and Th17 cells (p < 0.001) showed opposite trends. CDC42 was not related to Th1 cells (p = 0.134), positively correlated with Th2 cells (p = 0.023) and MMSE (p < 0.001), while negatively associated with Th17 cells (p < 0.001) in AD patients. CDC42 was only related to Th17 cells (p = 0.048) and MMSE (p = 0.048) in PD patients; and it was not linked with Th1, Th2, Th17 cells, or MMSE in HCs (all p > 0.05). During a 3-year follow-up, CDC42 was gradually declined in AD patients (p < 0.001), its decline was positively correlated with MMSE decline at 1 year (p = 0.004), 2 years (p = 0.005), and 3 years (p = 0.026).

Interpretation: CDC42 might have the potency to serve as a biomarker for estimating AD risk and progression.

Figure 1

Study flowchart.

Figure 2

Comparison of CDC42, Th1, Th2, and Th17 cells among AD patients, PD patients, and HCs. Comparison of CDC42 among AD patients, PD patients, and HCs (A), ROC curve analysis of CDC42’s ability to tell AD patients from PD patients (B) and from HCs (C). Comparison of Th1 cells (D), Th2 cells (E), and Th17 (F) among AD patients, PD patients, and HCs.

Figure 3

Correlation of CDC42 with Th1, Th2, and Th17 cells in AD patients, PD patients, and HCs. Correlation of CDC42 with Th1 cells (A), Th2 cells (B), and Th17 cells (C) in AD patients. Correlation of CDC42 with Th1 cells (D), Th2 cells (E), and Th17 cells (F) in PD patients. Correlation of CDC42 with Th1 cells (G), Th2 cells (H), and Th17 cells (I) in HCs.

Figure 4

Relation of CDC42 with MMSE score. Correlation of CDC42 with MMSE score at baseline in AD patients (A), PD patients (B), and HCs (C).

Figure 5

CDC42 was declined from baseline to 3 years in AD patients.

Figure 6

Correlation of CDC42 decline with MMSE decline in AD patients. Longitude changes of MMSE score during 3‐year follow‐up (A). Correlation between CDC42 decline and MMSE score decline at Y1 (B), Y2 (C), and Y3 (D).