Detection of a Unique Unfolded p53 Conformation (U-p53AZ) in Tissue of Alzheimers Disease Patients

Abstract

INTRODUCTIONAlzheimers Disease (AD) is a major public health challenge. An AD-specific unfolded form of the p53 protein was identified (U-p53AZ) and data from animal studies suggests it colocalizes with pTau, in neurofibrillary tangles (NFT) METHODSBrain samples of patients with AD, cognitively unimpaired non-AD, and with fronto-temporal dementia (FTD) are being tested, comparing the pattern of U-p53AZ accumulation (using the antibody 2D3A8, developed by Diadem SpA) with accumulation of pTau, beta-amyloid, and TDP-43. RESULTSU-p53AZ accumulates in brain samples from AD, colocalizes with pTau in the NFT, with a small degree of accumulation in neuritic plaques (NP). The intensity of staining correlates with the pTau staining and Braak staging. No staining is observed in samples from cognitively unimpaired non-AD and FTD. DISCUSSIONThis study provides further support to the hypothesis that U-p53AZ is a player in AD pathology, in link with pTau accumulation and Braak staging.