CNS neuroscience & therapeutics
Multimodal Characterization of APOE ε4-Associated Neurovascular Heterogeneity Using Retinal, Plasma, and Neuroimaging Biomarkers in Alzheimer's Disease
By Cheng H, Xia H, Wang Y and 6 others.
Abstract
Background
Biological heterogeneity remains a major challenge in Alzheimer's disease (AD), even among individuals with biomarker-confirmed disease. The apolipoprotein E (APOE) ε4 allele is associated with greater amyloid burden, neurodegeneration, and vascular dysfunction. We investigated whether retinal microvascular imaging provides complementary information beyond plasma and neuroimaging biomarkers for characterizing APOE ε4-associated neurovascular heterogeneity in biologically defined AD.
Methods
Eighty-four amyloid-positive patients with AD underwent color fundus photography, swept-source optical coherence tomography angiography (OCTA), plasma biomarker assessment, amyloid positron emission tomography, and magnetic resonance imaging. Retinal vascular parameters were compared between APOE ε4 carriers and non-carriers using generalized estimating equations. Candidate multimodal biomarkers were identified using least absolute shrinkage and selection operator (LASSO) regression, followed by multivariable logistic regression to evaluate the incremental contribution of retinal biomarkers within a multimodal phenotyping model.