Mitochondrial methylcytosines as blood-based biomarkers for Alzheimer's disease dementia prognosis.

ABSTRACT: Alzheimer's Disease Dementia (ADD) prognosis is an unmet medical need. Mitochondrial dysfunction is an early AD etiopathogenic factor. The present study analyzed mitochondrial DNA (mtDNA) methylation patterns in blood samples from patients with mild cognitive impairment (MCI) who progressed to ADD (P), MCI remained stable (NP), and Cognitively Normal (CN) individuals. Differentially methylated sites were identified in the D-loop region in both CN vs. NP and NP vs. P comparisons, even before β-amyloid positivity. A Random Forest model was developed using mtDNA methylation data combined with cognitive and risk factor features. Model's performance was assessed by cross-validation and tested on an independent set, achieving 84.4% accuracy in training and 83.2% (95% CI: 75.2%-89.4%) in testing.

SUBMITTER: Gascon-Bayarri J 

PROVIDER: S-EPMC12448035 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature