JKAP, Th1 cells, and Th17 cells are dysregulated and inter-correlated, among them JKAP and Th17 cells relate to cognitive impairment progression in Alzheimer's disease patients.

BACKGROUND

JNK pathway-associated phosphatase (JKAP) is engaged in Alzheimer's disease (AD) pathology via regulating immune response, cluster of differentiation 4 positive (CD4+) T cell differentiation, inflammation, and phosphorylated tau (p-tau). This study aimed to investigate its clinical value serving as a biomarker for AD.

METHODS

Fifty AD patients, 50 Parkinson's disease (PD) patients, and 50 controls (patients with non-degenerative neurological diseases with normal cognition) were enrolled. Their β-protein 42 (Aβ42), total tau (t-tau), p-tau, and Mini-Mental State Examination (MMSE) scale were assessed. Furthermore, JKAP in serum and T-help type 1 (Th1) and T-help type 17 (Th17) cells in CD4+ T cells were measured.

RESULTS

JKAP level was lower, while Th17 cell proportion (but not Th1 cell proportion) was higher in AD patients compared with PD patients and controls (all P < 0.01). Besides, JKAP level negatively correlated with both Th1 (r =  - 0.306, P = 0.030) and Th17 (r =  - 0.380, P = 0.006) cell proportions in AD patients but not PD patients and controls. Furthermore, in AD patients, JKAP positively correlated with Aβ42 (r = 0.307, P = 0.030) and MMSE score (r = 0.350, P = 0.013) while negatively correlated with p-tau (r =  - 0.280, P = 0.048); Th17 cell proportion negatively associated with Aβ42 (r =  - 0.281, P = 0.048) and MMSE score (r =  - 0.366, P = 0.009). Notably, JKAP was negatively related to 1-year (r =  - 0.297, P = 0.038) and 2-year MMSE decline (r =  - 0.304, P = 0.048); Th17 cell proportion was positively linked with 1-year (r = 0.392; P = 0.008), 2-year (r = 0.482, P = 0.001), and 3-year (r = 0.365, P = 0.013) MMSE decline.

CONCLUSION

JKAP, Th1 cells, and Th17 cells are dysregulated and inter-correlated; among them, JKAP and Th17 cells relate to cognitive impairment progression in AD patients.