Plasma Glial Fibrillary Acidic Protein and Neurofilament Light Chain Concentrations Are Inversely Associated with Retinal Microvascular Perfusion and Vessel Density in Cognitively Normal Individuals with Familial or Genetic Risk Factors for Alzheimer's Disease.

Background/Objectives: Evaluating noninvasive, accessible ocular and blood-based biomarkers could aid in early risk stratification and disease detection during the preclinical phase of Alzheimer's disease. This study investigates associations between plasma biomarkers of neurodegeneration and retinal structural and microvasculature parameters in cognitively normal adults with familial or genetic risk factors for Alzheimer's disease. Methods: Forty-one participants underwent plasma sampling for glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid-beta42 (β42), amyloid-β42/40 ratio, and phosphorylated-tau217 (p-tau217), and also underwent optical coherence tomography (OCT) and OCT angiography (OCTA) imaging. Apolipoprotein E genotyping and family history of Alzheimer's disease were recorded. Generalized estimating equations adjusting for age, sex, race, treated hypertension, Alzheimer's disease family history, and APOE ε4 carrier status assessed associations between plasma biomarker concentrations and OCT and OCTA measurements. Results: Higher plasma GFAP and NfL concentrations were significantly associated with reduced superficial capillary plexus perfusion density and vessel density on macular OCTA. In additional analyses restricted to participants with plasma biomarker and retinal imaging assessments obtained within 9 months, associations with GFAP remained significant, whereas NfL associations no longer remained significant after correction for multiple comparisons. Conclusions: Retinal OCTA and OCT metrics may reflect general neurovascular aging in cognitively normal individuals with familial or genetic risk factors for Alzheimer's disease.