Association of Retinal Nerve Fiber Layer Thickness with Plasma pTau181 and Aβ42/Aβ40 ratio

Abstract

AbstractBackgroundThe eye has been considered a ‘window to the brain’ and to several neurodegenerative brain disorders including Alzheimer’s disease (AD) that display alterations in the eye, especially the retina. Plasma levels of AD biomarkers, including pTau181 and Aβ42/Aβ40 ratio are significantly altered in AD patients. We sought to evaluate the association of peripapillary retinal nerve fiber layer (RNFL) thickness measured using optical coherence tomography (OCT) with plasma levels of pTau181 and the Aβ42/Aβ40 ratio.MethodParticipants (78; 21 mild cognitive decline/AD, 27 subjective cognitive decline and 30 cognitively normal) underwent ophthalmological evaluation including OCT and a blood sample. Single molecule array (Simoa) assays were used to measure plasma concentrations of pTau181, Aβ42, and Aβ40 at the University of Gothenburg. Partial Pearson correlations, covaried for age and sex, were used to compare thickness of the peripapillary retinal nerve fiber layer (RNFL) with plasma level of pTau181 and the ratio of Aβ42/Aβ40.ResultPlasma pTau181 was significantly associated with RNFL thickness in the superior quadrant of the retina in the right eye (rp=‐0.300, p=0.025) and showed a trend towards an association with mean RNFL thickness of the right eye (rp= ‐0.226, p=0.094). Plasma Aβ42/Aβ40 showed a significant positive association with nasal RNFL of the right eye (r=0.312, p=0.027), as well as a negative association with RNFL thickness in the temporal quadrant of both eyes (right: r=‐0.324, p=0.022; left r=‐0.325, p=0.021).ConclusionThe majority of the sample was cognitively normal or mildly impaired, suggesting that RNFL thickness may be a useful tool for early diagnosis of AD‐related pathophysiology. Future longitudinal studies in larger samples and evaluating the utility of combining retinal and plasma biomarkers for predicting future progression to AD are needed.