Background: Alzheimer’s disease (AD) cannot be diagnosed until dementia appears, thus the detection of early disease-related biomarkers is crucial to facilitate the development of new diagnostic tools and drug therapies. Candidate biochemical markers for AD should be molecules representing some of the cerebral pathogenetic processes typical of AD. Alternatively they should represent altered metabolic or cellular processes in the brain or in peripheral tissues from affected patients. In research of secondary markers we recently found an intriguing correlation between p53 and AD. In particular, we demonstrated that fibroblasts from sporadic AD patients specifically express an unfolded and detectable conformational state of p53 that allows to differentiate them from fibroblasts of age-matched non-AD subjects (Uberti et al., 2006). Methods: In this study, we used a rapid and easy flow-cytometric approach to investigate the different expression of conformationally altered p53 between AD and non-AD subjects on peripheral blood cells, which represent a more accessible cellular model than fibroblasts. We enrolled more than 150 subjects and tested the content of unfolded p53 in AD, non AD and subjects affected by other dementia. Results: We found that peripheral blood cells from AD specifically expressed increased levels of unfolded p53 in comparison with non AD subjects. A statistically significant correlation was observed when the expression of unfolded p53 and the age of both control subjects and AD patients were considered thus demonstrating that altered p53 is an age-dependent factor. In order to evaluate the diagnostic performance of unfolded p53 as an AD trait marker, we calculated sensitivity and specificity within different age intervals and we found that these values were more significant in subjects up to 70 years of age compared to the values in individuals older than 70 years. Within this specific age interval (< 70 years), sensitivity and specificity were respectively 90% and 77%. Conclusions: The observation of an altered p53 content in young patients is of great importance and could suggest the usefulness of this method especially for younger people, thus supporting its putative application for subjects with mild cognitive impairment (MCI) and with early onset of AD.
