Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Discovery of Simple Blood-Based Test to Predict Early Onset of Alzheimer’s Using Standard Clinical Mass Spectrometry Platforms

Version 1 : Received: 25 January 2021 / Approved: 26 January 2021 / Online: 26 January 2021 (10:01:35 CET)

How to cite: Piccirella, S.; Cristoni, S.; Fowler, C.; Doecke, J.; Abate, G.; Uberti, D. Discovery of Simple Blood-Based Test to Predict Early Onset of Alzheimer’s Using Standard Clinical Mass Spectrometry Platforms. Preprints 2021, 2021010530. https://doi.org/10.20944/preprints202101.0530.v1 Piccirella, S.; Cristoni, S.; Fowler, C.; Doecke, J.; Abate, G.; Uberti, D. Discovery of Simple Blood-Based Test to Predict Early Onset of Alzheimer’s Using Standard Clinical Mass Spectrometry Platforms. Preprints 2021, 2021010530. https://doi.org/10.20944/preprints202101.0530.v1

Abstract

Despite the increasing number of individuals affected by Alzheimer’s disease (AD) every year, no effective therapy has been developed to treat this neurodegenerative disease yet. The current methods for AD diagnosis are effective for clinical confirmation of the disease only when symptoms become apparent, years after molecular damage started within the patients’ brains. As higher expression of a conformationally altered p53 has been correlated with AD, we developed a mass spectrometry-based method for highly sensitive, specific, and reproducible quantification of a p53 conformational variant in plasma samples of patients with known clinical outcome. In particular, we tested the prognostic performance of an AD-specific 2D3A8-immunoselected p53 peptide (AZ 284™) in different sets of individuals progressing from both cognitively unimpaired (CU) and mild cognitive impairment (MCI) patients progressing to AD dementia. Our data showed that quantitative analysis of AZ 284™ is a reliable tool for predicting AD progression up to 6 years prior to dementia onset with AUC >90%. Taken together, these results support the implementation of p53 conformational variant quantification as an affordable and powerful diagnostic tool for early, non-invasive AD diagnosis.

Keywords

Alzheimer’s disease; biomarker; prognosis; P53; mass spectrometry

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Comments (0)

Comment 1
Received: 26 January 2022
Commenter: Nurfarah Aqilah binti Ahmad Nizam
The commenter has declared there is no conflict of interests.
Comment: Dear authors,

Congratulations on the awesome discovery. I would really like to include this technology in the assessment of emerging technologies of our unit of Horizon Scanning, Health Technology Assessment.

However, I would really like to know the status of your previous pre-print paper (Performance of a non-invasive blood test for a conformational variant of p53 to predict Alzheimer's disease within 6 years of clinical diagnosis and A conformational variant of p53 (U-p53AZ) as blood-based biomarker for the prediction of the onset of symptomatic Alzheimer's disease. May I know the reason that this paper not published yet?

You can reach me by email aqilah.nizam@moh.gov.my

Thank you
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