Document Type
Article
Publication Date
4-1-2026
Original Citation
Chong Chie J,
Persohn S,
Pandey R,
Simcox O,
Carter GW,
Salama P,
Territo P,
.
Multiscale metabolic covariance networks uncover stage-specific biomarker signatures across the Alzheimer's disease continuum. Alzheimers Dement. 2026;22(4):e71218.
Keywords
JGM, Humans, Alzheimer Disease, Female, Biomarkers, Male, Disease Progression, Brain, Retrospective Studies, Connectome, Positron-Emission Tomography, Aged, 80 and over, Magnetic Resonance Imaging, Sex Characteristics
JAX Source
Alzheimers Dement. 2026;22(4):e71218.
ISSN
1552-5279
PMID
42047294
DOI
https://doi.org/10.1002/alz.71218
Grant
Data collection and sharing for this project was funded by the ADNI (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012).
Abstract
INTRODUCTION: Functional connectomics studies leverage the power of interregional brain relationships using graph theory of glycolytic metabolism to establish neural connections and their roles in cognition and disease and to monitor therapeutic responses.
METHODS: Using a retrospective clinical population (N = 431) from ADNI, we evaluated disease changes using metabolic covariance analysis. In addition, we developed a novel region set enrichment analysis (RSEA) to detect brain functional changes based on metabolic variations. Results were aligned with transcriptomic signatures and clinical cognitive assessments (CCAs).
RESULTS: Our findings highlight sexual dimorphic changes across the disease spectrum, which suggest brain network reorganization occurs as compensatory mechanisms due to pathological disruptions. RSEA indicated functional changes in motor, memory, language, and cognitive functions related to disease progression, and these changes were supported by transcriptomic signatures.
DISCUSSION: Together, metabolic covariance analysis, regional connectomics, and RSEA allow for AD progression tracking and functional alteration identification based on metabolic readouts, consistent with CCA.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.