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Alzheimer's disease-like brain pattern biomarker: capturing risks and predicting disease onset.
Peter Kochunov1,2, Si Gao3, Lauren E Salminen4
1Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. peter.kochunov@uth.tmc.edu.
Molecular Psychiatry
|April 27, 2026
Summary
A new Regional Vulnerability Index (RVI-AD) shows early Alzheimer's disease (AD) changes in healthy individuals. This biomarker detects risks from APOE-e4 and cardiovascular factors, predicting future dementia conversion.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Gerontology
Background:
- Alzheimer's disease (AD) prevention necessitates early detection through reliable biomarkers.
- Existing methods struggle to identify subtle, preclinical AD brain changes.
- Individual brain vulnerability to AD pathology remains poorly quantified.
Purpose of the Study:
- To develop and validate a novel Regional Vulnerability Index (RVI-AD) for quantifying individual brain similarity to AD-related deficit patterns.
- To assess the association of RVI-AD with genetic (APOE-e4) and cardiovascular (FCVRS) risk factors in diverse cohorts.
- To evaluate RVI-AD's predictive capability for the conversion from mild cognitive impairment (MCI) to dementia.
Main Methods:
- Calculated regional effect sizes to define AD brain deficit patterns in amyloid-positive AD cases versus controls.
- Computed RVI-AD as a linear index of individual brain pattern similarity to established AD deficits.
- Validated RVI-AD in the Amish Connectome Project (N=335), UK Biobank (N=26,010), and Alzheimer's Disease Neuroimaging Initiative (ADNI, N=1932) cohorts.
Main Results:
- Healthy individuals with APOE-e4 showed significantly elevated RVI-AD (p < 0.05).
- FCVRS interacted with APOE-e4 to significantly increase RVI-AD (p < 10^-4).
- RVI-AD predicted MCI to dementia conversion in ADNI (AUC=70-74%, OR=2.16, p < 10^-16).
Conclusions:
- RVI-AD effectively detects the impact of AD risk factors (APOE-e4, cardiovascular) in normally aging individuals.
- Elevated RVI-AD predicts future dementia conversion, particularly within the first three years.
- RVI-AD shows potential as a noninvasive, accessible biomarker for early AD detection and risk stratification.
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