AlzoSure® Predict, a simple minimally‐invasive blood test to predict the early onset of Alzheimer’s disease before the manifestation of clinical symptoms

Abstract

AbstractBackgroundOngoing research seeks to identify blood‐based biomarkers able to predict the onset and progression of Alzheimer’s disease (AD). AlzoSure® Predict is a rapid, minimally‐invasive blood test that predicts the early onset of AD up to, at least, 6 years in advance of clinical symptoms.MethodsThe AlzoSure® Predict test, an IP‐LC‐MS/MS based method, was performed to quantify the AZ284® peptide of an unfolded variant of the p53 protein (U‐p53AZ). The data were compared with the neuropsychological diagnosis in a longitudinal cohort of 479 subjects between 60 and 85 years old from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study. The cohort consists of 237 cognitive normal, including both subjects with no and subjective memory complaints (NMC/SMC) and 98 mild cognitive impairment (MCI), 141 AD, and 3 other dementia patients that were followed‐up every 18 months.ResultsThe data confirms the strong diagnostic value of U‐p53AZ with a sensitivity of 95% for AD, discriminating it from NMC and SMC subjects with an AUC of 99.8% (95% CI: 99.6‐100.0%) and a specificity of 99.6%, and from MCI patients at the early symptomatic stage with an AUC of 95.7% (95% CI: 92.8‐98.5%) and a specificity of 91.8%.In the prognostic setting, U‐p53AZ showed a significantly better performance (P<0.0001) with an AUC of 99.0% (95%CI: 98.2‐99.8%) compared to amyloid b‐PET (Ab‐PET) with an AUC of 83.5% (95% CI: 79.5‐87.5%). Due to unavailability of data, Ab‐PET performance was determined on a subset of 422 subjects. In a multifactorial Cox proportional hazards model, U‐p53AZ proved to be the major contributor and and the best performing, independent predictor for cognitive decline to neuropsychological AD over time. In this model with normalized continuous risk factors, U‐p53AZ was the most significant contributor (P<.0001) with a hazards ratio of 2.92, compared to Aβ‐PET (P<.0155), APOE ε4 (P<.2323), and age (P<.0106).ConclusionThe present study confirms the diagnostic performance of U‐p53AZ for AD and expands its potential into the prognostic field. Additional studies are going to be performed based on both ADRC and ADNI samples to further prove the prognostic power and the utility of the AlzoSure® Predict test.