A NEW PUTATIVE EARLY BIOMARKER FOR A BLOOD-BASED TIMELY DIAGNOSIS FOR ALZHEIMER’S DISEASE

Abstract

Although Alzheimer's disease (AD) is commonly regarded as a disease of the brain, it is now recognized that AD is a systemic disease that affects peripheral tissues outside the central nervous system, from the earliest stages of the disease. Given its multifactorial nature, the timely diagnosis of sporadic AD is challenging. There is a clear need for the development of a simple, inexpensive, minimally invasive test for AD to diagnose the disease, ideally at its earliest stages. In the research of blood-based signatures for timely diagnosis of AD, oxidative stress biomarkers have been intensively investigated. Peculiar oxidative-end products can allow the identification of those early oxidative alterations that anticipate the establishment of an overt oxidative stress. In this contest an open isoform of p53 protein (unfolded p53), resulting from nitration to its tyrosine residues, resulted high sensitive to redox environmental alterations and was found peculiarly high expressed in blood cells derived from familiar and sporadic AD. A new conformational specific anti-human p53 antibody has been validated in nearly 300 subjects, including AD, Mild Cognitive Impairment (MCI) patients and age-matched controls, by measuring unfolded p53 with a standardized and reproducible ELISA assay. Unfolded p53 expression resulted higher in plasma of both AD and MCI patients compared to healthy subjects, while in peripheral blood mononuclear cells (PBMCs) unfolded p53 was found increased only in the AD group of patients. Unfolded p53 has been also tested to screen the 4 years follow up patients and it has been useful to predict MCI to AD transition. Although further studies are still necessary for validating unfolded p53 as a potential redox biomarker for AD, the availability of a standardized assay might allow the collection of additional data from different scientific groups. This could be an interesting starting point for a reliable AD-blood-based test that can aid in the timely diagnosis of AD.