Diagnostic Performance of the AlzoSure Predict Assay and Its Association With Alzheimer's Disease Biomarkers and Imaging Findings

ABSTRACT Background Early diagnosis of Alzheimer's disease (AD) is critical for improving patient outcomes. The laboratory‐developed blood test of AlzoSure measures the unfolded conformational variant of p53 (U‐p53AZ) in plasma and has shown promise as a screening tool for AD risk. We aimed to evaluate the association between U‐p53AZ with established cerebrospinal fluid (CSF) and neuroimaging measures, and to determine its diagnostic performance in distinguishing cognitively normal (CN) individuals from those with mild cognitive impairment (MCI). Methods Participants included CN and MCI individuals aged 55–90 years with complete baseline and 24‐month follow‐up assessments. Associations between U‐p53AZ, CSF biomarkers, standardized uptake value ratio (SUVR) of glucose measured by fluorodeoxyglucose positron emission tomography (FDG‐PET), and cognition were examined with multivariable regression models adjusted for age, sex, and APOE ε4 status. Diagnostic performance was assessed with receiver operating characteristic (ROC) analysis. Results At baseline, no significant group differences were observed in plasma U‐p53AZ, FDG SUVR, or CSF biomarkers between CN and MCI. Longitudinally, FDG SUVR significantly declined in MCI ( p = 0.040), while CSF t‐tau and p‐tau181 increased in both groups (all p < 0.05). Higher U‐p53AZ levels were independently associated with elevated CSF t‐tau ( β = 0.38; p = 0.033) and p‐tau181 ( β = 0.37; p = 0.033) at baseline, and these associations persisted at follow‐up ( β range 0.43–0.48; all p < 0.02). No significant associations were found with FDG SUVR or cognitive scores. The discriminative ability of U‐p53AZ to distinguish CN from MCI was modest (AUC = 0.617, 95% CI 0.518–0.716). Conclusion AlzoSure measurements are significantly associated with CSF tau values but demonstrate limited utility in differentiating CN from MCI. Although promising as a marker of tau‐related neurodegeneration, AlzoSure has a modest diagnostic performance as a stand‐alone assessment.