Association Between U‐p53AZ Blood Biomarker and White Matter Microstructure in Early Alzheimer's Disease: A Cross‐Sectional Study Using AlzoSure® Predict
Bibliographic record
Abstract
Background and Aims: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by early microstructural white matter (WM) damage, often preceding clinical symptoms. While cerebrospinal fluid (CSF) biomarkers provide valuable insights into AD pathology, they are invasive and may not reflect early WM changes. U-p53AZ, a conformational variant of p53 detected via the AlzoSure® blood assay, has emerged as a potential biomarker for early AD detection. This study aimed to investigate the association between AlzoSure® prediction scores and WM microstructural integrity in cognitively normal (CN) individuals and those with mild cognitive impairment (MCI), using diffusion tensor imaging (DTI). Secondary analyses explored parallels with established CSF biomarkers (Aβ₁₋₄₂, total tau, and p-tau181). Methods: We analyzed data from 106 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (46 CN, 60 MCI) with available DTI and biomarker data. AlzoSure® scores were derived from plasma samples using immunoprecipitation. DTI metrics (fractional anisotropy, mean, axial, and radial diffusivity) were extracted from atlas-defined WM regions. Linear regression models, stratified by diagnosis and adjusted for age, gender, and polygenic hazard score, were used to examine associations between biomarkers and DTI indices. False discovery rate (FDR) correction was applied for multiple comparisons. Results: In the MCI group, higher AlzoSure® scores were significantly associated with reduced diffusivity metrics in the left cingulum hippocampal bundle, a region implicated in early AD-related disconnection. Parallel associations were observed with CSF t-tau and p-tau181 across other WM tracts in MCI. However, no associations remained significant after FDR adjustment. Conclusion: These findings underscore the potential of U-p53AZ, as measured by AlzoSure®, to capture early WM microstructural alterations particularly in individuals with MCI, aligning with tau-related pathology patterns. While exploratory, the results highlight U-p53AZ as a non-invasive candidate biomarker for early AD-related neurodegeneration. Larger, longitudinal studies are needed to validate its diagnostic and prognostic utility in preclinical and prodromal AD stages.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".