Conformation of P53 protein in peripheral lymphocytes from Alzheimer's disease patients

Abstract

Objective To detect the conformational state of P53 protein in peripheral blood lymphocytes from Alzheimer's disease (AD) subjects, and explore a novel blood biomarker of AD. Methods Eighteen AD patients, admitted to our hospital from June 2011 to June 2016, were used as experimental group; 14 patients with vascular dementia (VaD) and 12 patients with other central nervous system degenerative disease such as Parkinson's disease and Parkinsonism-plus syndrome (PD/PPS) who showed dementia, and 18 healthy subjects were selected as three control groups. Peripheral blood of 2 mL was extracted from all subjects, and lymphocytes were extracted; the conformational state of P53 protein in lymphocytes was evaluated by immunofluorescent staining with conformation-specific monoclonal antibodies: PAb1620 (specific for wild-type conformation) and PAb240 (specific for mutant-type conformation). After PAbl620(+) cells and PAb240(+) cells were selected, flow cells technology was used to evaluate cell cycle distribution. Results (1) P53 proteins of wild-type conformation and mutant-type conformation were noted in four groups, with significant differences (F=452.713, P=0.000; F=1240.846, P=0.000): expressions of P53 proteins of wild-type conformation and mutant-type conformation in experimental group were significantly stronger than those in the other three groups (P< 0.05). (2) Ratio of 1620/240 cells showed significant differences in the four groups (F=112.534, P= 0.000): that in the experimental group was significantly stronger than that in the other three groups (P< 0.05). (3) G1% was statistically lower and S% was significantly higher in PAb240(+) cells as compared with those in the PAb1620 (+) cells (P<0.05). Conclusions Lymphocytes from AD subjects can express anomalous and detectable mutant-like P53 protein which makes these cells being distinct from cells of controls. A closely putative link is shown between mutant-like P53 protein and dysfunction of G1/S checkpoint in lymphocytes from AD. This mutant-like p53 protein in peripheral blood lymphocytes might be unique to AD, which is expected to be a novel blood biomarker for AD, as well as to provide a new target for AD therapy. Key words: Alzheimer's disease; Lymphocyte; P53; Conformation; Biomarker