Combination of p53(ser15) and p21/p21(thr145) in peripheral blood lymphocytes as potential Alzheimer's disease biomarkers

Alzheimer's disease (AD) is still difficult to be precisely diagnosed in its early stage to date. Establishing of reliable and manageable disease-specific biological markers is required to improve diagnostic accuracy. Based on the hypothesis of cell cycle regulatory failure at the early stage of AD, we tested whether cell cycle regulating proteins p53, p21 and their phosphorylated forms p53(ser15), p21(thr145) were changed in AD patients and whether these proteins could be used as diagnostic biomarkers. Western bolt, Enzyme-linked immunosorbent assay (ELISA), immunofluorescent staining and flow cytometry (FCM) analysis were employed to analyze levels of these proteins in peripheral blood lymphocytes (PBLs) from 95 controls, 94 AD, 12 Parkinson's disease (PD) and 15 vascular dementia (VaD) patients. Compared with controls, p53(ser15) and p21(thr145) levels were significantly increased and p21 level was significantly decreased in PBLs of AD patients but not in PD or VaD, while p53 was increased in both AD and VaD patients. The receiver operating characteristic (ROC) curve analysis showed that the specificity and sensitivity were 76% and 84% for p53, 88% and 82% for p53(ser15), 80% and 75% for p21 and 84% and 68% for p21(thr145) in identifying AD patients. The relatively high diagnostic accuracy support these proteins, especially p53(ser15) and p21 in PBLs may become potential biomarkers for diagnosis of AD.