Detection of a Unique Unfolded p53 Conformation (U-p53AZ) in the Tissue of Alzheimer’s Disease Patients

  1. David Lynch
  2. Sam Agus
  3. Rakez Kayed
  4. Michael Rasche
  5. Madison Samples
  6. Simona Piccirella
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Abstract

INTRODUCTION

Alzheimer’s 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)

METHODS

Brain 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.

RESULTS

U-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.

DISCUSSION

This study provides further support to the hypothesis that U-p53AZ is a player in AD pathology, in link with pTau accumulation and Braak staging.

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