Perifoveal Choriocapillaris Flow Deficits AssociatedWith Cerebrospinal Fluid Aβ42/tau in Presymptomatic Alzheimer’s Disease

Abstract

Purpose: This study investigated the association between swept-source OCTA (SS-OCTA) choriocapillaris flow deficit percentage (CC FD%) and cerebrospinal fluid (CSF) biomarkers in presymptomatic Alzheimer’s disease (AD). Methods: Twenty-three cognitively healthy (CH) participants, including those with pathological (CH-PAT) and normal (CH-NAT) Aβ42/tau ratios, underwent lumbar puncture for CSF Aβ42/tau and ptau-181 quantification using electrochemiluminescence assays. OCTA en face images of the choriocapillaris were analyzed for flow deficits within a 6 × 6 mm macular grid and 3-and 6-mm Early Treatment of Diabetic Retinopathy Study (ETDRS) perifoveal rings. The association between CC FD% and CSF Aβ42/tau and CSF ptau-181 levels was evaluated. Results: Perifoveal microvascular changes in the choriocapillaris outer ring (6-mm ETDRS ring) were significantly correlated with the CSF Aβ42/tau ratio in CH-PATs compared to CH-NATs. However, linear regression analysis across all CH participants (CH-PAT + CH-NAT) revealed that only age was significantly associated with CSF ptau-181 levels. Conclusions: Our findings suggest that this cohort is in an early preclinical AD stage, without ptau-181 biomarker evidence of established AD. SS-OCTA measures may complement CSF A/T (amyloid/tau) levels, helping to define transitional stages from CH-NAT to CH-PAT during presymptomatic AD. Translational Relevance: By identifying the transition from normal aging to presymptomatic AD, SS-OCTA metrics combined with biofluid markers could enhance AD oculomics by stratifying disease risk and prioritizing treatment interventions.