Cerebrospinal fluid amyloid-β 42/40 ratio is associated with ganglion cell-inner plexiform layer thinning in individuals with and without amyloid pathology

Abstract

Background

Retinal imaging offers a noninvasive window into neurodegenerative changes, yet its relationship with established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) remains poorly understood. This study addresses a critical gap by examining whether retinal structural findings on optical coherence tomography (OCT) correlate with CSF biomarkers of AD pathology and neurodegeneration.

Objective

To determine if CSF biomarkers correlate with retinal OCT imaging findings in individuals with AD.

Methods

In this cross-sectional study, subjects underwent lumbar puncture for CSF collection and were imaged using the Zeiss Cirrus HD-5000 with AngioPlex.

Results

Forty participants (73 eyes) were included in this study. Twenty-one had normal cognition and negative CSF AD biomarkers, 12 had normal cognition and positive CSF AD biomarkers, and seven had mild cognitive impairment. Central subfield thickness (CST), retinal nerve fiber layer (RNFL), and ganglion cell inner plexiform layer (GCIPL) thicknesses were associated with CSF amyloid-β 42/40 ratio (Aβ_42/40), phosphorylated tau at threonine 181 (pTau181)/Aβ₄₀ ratio, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) using multivariable generalized estimating equations. There were no statistically significant associations between CSF pTau181/Aβ₄₀ ratio, NfL, or GFAP and CST, GCIPL thickness, or RNFL thickness (p > 0.05 for all). Aβ_42/40 ratio was positively associated with GCIPL thickness (p = 0.02), but not with CST or RNFL thickness (p = 0.31 and p = 0.82, respectively).

Conclusions

Decreased CSF Aβ_42/40 ratio, a biomarker of amyloid plaque pathology, is associated with decreased GCIPL thickness. GCIPL thinning may correspond with CSF abnormalities consistent with amyloid pathology that is present even prior to cognitive decline.