ArticleAlzheimer's & dementia (New York, N. Y.)
Hippocampal mediation in the lipid-Alzheimer's disease pathway: A high-dimensional mediation analysis stratified by
Article in Alzheimer's & dementia (New York, N. Y.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionSystemic lipid dysregulation is a modifiable risk factor for Alzheimer's disease (AD), yet the neuroanatomic pathways through which specific lipids influence AD progression remain poorly delineated. We investigated whether brain structure mediates the relationship between plasma lipids and AD progression, and whether this pathway is modified by apolipoprotein E (
methodsThis retrospective cohort study included 1019 non-demented participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Baseline plasma lipidomics (781 species) and subsequent T1 magnetic resonance imaging (MRI)-derived brain volumes and cortical thickness (198 features) were analyzed. Cox models identified lipids and brain regions associated with time-to-AD progression. High-dimensional mediation analysis (HIMA) was employed to identify significant mediators, followed by stratified analyses by
resultsThirty-five lipids were associated with AD progression. High-dimensional mediation analysis across all 198 imaging features uniquely identified left hippocampus volume as the sole significant mediator for 14 specific lipids, including lysophosphatidylcholines and phosphoinositols. Stratified analyses revealed that this mediation pathway was predominantly driven by DISCUSSION: The left hippocampus is a critical mediator linking specific plasma lipids to AD progression, with an additional vascular pathway via white matter hyperintensities emerging after comorbidity adjustment. This pathway is strongly modified by both
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