Conformationally altered p53: a putative peripheral marker for Alzheimer's disease

The identification of biological markers of Alzheimer's disease (AD) can be extremely useful to improve diagnostic accuracy and/or to monitor the efficacy of putative therapies. In this regard, peripheral cells may be of great importance because of their easy accessibility. After subjects were grouped according to diagnosis, the expression of conformational mutant p53 in blood cells was compared by immunoprecipitation or by a cytofluorimetric assay. One hundred and four patients with AD, 92 age-matched controls, 15 patients with Parkinson's disease, and 9 with other types of dementia were analyzed. Two independent methods to evaluate the differential expression of a conformational mutant p53 were developed. Mononuclear cells were analyzed by immunoprecipitation or by flow cytometric analysis, following incubation with a conformation-specific p53 antibody, which discriminates unfolded p53 tertiary structure. Mononuclear cells from AD patients express a statistically significantly higher amount of mutant-like p53 compared to mononuclear cells from non-AD subjects, thus supporting the study of conformational mutant p53 as a new putative marker to discriminate AD from non-AD patients. We also observed a strong positive correlation between the expression of p53 and the age of patients. The expression of mutant p53 did not correlate with the duration of illness and the Mini Mental State Examination scores.