Retinal ganglion cell dysfunction in preclinical Alzheimer\u2019s disease: an electrophysiologic biomarker\xa0signature

Samuel Asanad,Rustum Karanjia,Michele Fantini,Christian M Felix,Alfredo A Sadun,Michael G Harrington

doi:10.1038/s41598-021-85010-1

Abstract

The current study evaluated retinal function using electroretinography (ERG) in cognitively healthy (CH) participants with preclinical Alzheimer’s disease (AD), as classified by cerebral spinal fluid (CSF) Aβ42/Tau ratio. Individuals with normal retinal morphology ascertained by spectral-domain optical coherence tomography were enrolled. Full-field ERG, pattern PERG, and photopic negative response (PhNR) were performed in 29 adult participants (58 eyes). Amplitude and implicit times of the ERG wave components were analyzed. Preclinical AD participants showed marked retinal ganglion cell dysfunction relative to controls. The PhNR was significantly diminished in preclinical AD relative to controls. PhNR amplitude and N95 implicit time differentiated CH individuals with CSF biomarkers of AD pathology with 87% sensitivity and 82% specificity. These quantitative electrophysiologic findings expand our understanding of early retinal functional changes that precede cognitive decline in AD. Retinal ganglion cell dysfunction, as detected by ERG, may be a clinically useful, non-invasive in vivo biomarker for early disease detection, which is necessary for ultimately pursuing early intervention.

Highlights

The current study evaluated retinal function using electroretinography (ERG) in cognitively healthy (CH) participants with preclinical Alzheimer’s disease (AD), as classified by cerebral spinal fluid (CSF) Aβ42/Tau ratio
A recent prospective study conducted by our group demonstrated significant retinal thinning in preclinical AD participants who were biochemically confirmed for abnormal CSF Aβ42/Tau[31]
The present study evaluates, for the first time, retinal function using ERG in preclinical AD participants with structurally normal optical coherence tomography (OCT) and investigates whether retinal electrophysiologic data can help discriminate between CH individuals with normal versus pathological Aß42/Tau ratio

Summary

Introduction

The current study evaluated retinal function using electroretinography (ERG) in cognitively healthy (CH) participants with preclinical Alzheimer’s disease (AD), as classified by cerebral spinal fluid (CSF) Aβ42/Tau ratio. PhNR amplitude and N95 implicit time differentiated CH individuals with CSF biomarkers of AD pathology with 87% sensitivity and 82% specificity These quantitative electrophysiologic findings expand our understanding of early retinal functional changes that precede cognitive decline in AD. In addition to progressive memory loss and cognitive decline[3], ophthalmologic impairments in contrast sensitivity, color discrimination, and motion perception have been reported in AD4 These symptoms of visual dysfunction in AD cannot be explained by cortical deficits alone and have been associated with the degeneration of anterior visual pathways, namely the optic nerve and the retina[5,6,7,8,9,10]. The present study evaluates, for the first time, retinal function using ERG in preclinical AD participants with structurally normal OCTs and investigates whether retinal electrophysiologic data can help discriminate between CH individuals with normal versus pathological Aß42/Tau ratio

Methods

Results

Conclusion