A Conformational Variant of p53 (U-p53AZ) as Blood-Based Biomarker for the Prediction of the Onset of Symptomatic Alzheimer’s Disease - 21/11/24
, L. Van Neste 2, C. Fowler 1, C.L. Masters 3, J. Fripp 4, J.D. Doecke 4, C. Xiong 5, D. Uberti 6, 7, P. Kinnon 1
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Abstract |
Background |
Ongoing research seeks to identify blood-based biomarkers able to predict onset and progression of Alzheimer’s disease (AD).
Objective |
The unfolded conformational variant of p53 (U-p53AZ), previously observed in AD individuals, was evaluated in plasma samples from individuals participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) cohort for diagnostic and prognostic assessment, validated on a neuropsychological-based diagnosis, over the course of six years.
Design |
Retrospective Longitudinal Prognostic biomarker study.
Setting |
Single-center study based on the AIBL cohort.
Participants |
482 participants of the AIBL cohort, aged 60–85 years, without uncontrolled diabetes, vascular disease, severe depression or psychiatric illnesses.
Measurements |
The AlzoSure® Predict test, consisting of immunoprecipitation (IP) followed by liquid chromatography (LC) tandem mass spectrometry (MS/MS), was performed to quantify the AZ 284® peptide as readout of U-p53AZ and compared with an independent neuropsychological diagnosis. The amyloid load via amyloid β-positron emission tomography (Aβ-PET) and supporting clinical information were included where possible.
Results |
U-p53AZ diagnostic and prognostic performance was assessed in both time-independent and time-dependent (36, 72 and 90 months following initial sampling) analyses. Prognostic performance of Aβ-PET and survival analyses with different risk factors (gender, Aβ-PET and APOE ε4 allele status) were also performed. U-p53AZ differentiated neuropsychologically graded AD from non-AD samples, and its detection at intermediate/high levels precisely identified present and future symptomatic AD. In both time-independent and time-dependent prognostic analyses U-p53AZ achieved area under the curve (AUC) >98%, significantly higher than Aβ-PET AUCs (between 84% and 93%, P respectively <0.0001 and <0.001). As single factor, U-p53AZ could clearly determine the risk of AD neuropsychological diagnosis over time (low versus intermediate/high U-p53AZ hazard ratio=2.99). Proportional hazards regression analysis identified U-p53AZ levels as a major independent predictor of AD onset.
Conclusions |
These findings support use of U-p53AZ as blood-based biomarker predicting whether individuals would reach neuropsychologically-defined AD within six years prior to AD diagnosis. Integration of U-p53AZ in screening processes could support refined participant stratification for interventional studies.
Le texte complet de cet article est disponible en PDF.Key words : Alzheimer’s disease, blood-based biomarker, AD, p53, prognosis, U-p53
Plan
| How to cite this article: S. Piccirella, L. Van Neste, C. Fowler, et al. A Conformational Variant of p53 (U-p53AZ) as Blood-Based Biomarker for the Prediction of the Onset of Symptomatic Alzheimer’s Disease. J Prev Alz Dis 2022;3(9):469-479; jpad.2022.52 |
Vol 9 - N° 3
P. 469-479 - juillet 2022 Retour au numéro
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