Nonvascular Retinal Imaging Markers of Preclinical Alzheimer’s Disease

Abstract

Purpose : Successful treatment of Alzheimer’s disease (AD) requires early detection. It is known that individuals with symptomatic AD have beta-amyloid (Aβ) plaques in the brain and concomitant accumulation of Aβ plaques in the retina.^1,2 In the preclinical stage of AD there is accumulation of neocortical Aβ plaques. The aim of this study was to characterize early structural retinal changes in preclinical AD.

Methods : Sixty-three adults aged 55-75 with a self-reported first degree family member with AD and subjective memory complaint underwent ¹⁸F-florbetapir PET to quantify the degree of neocortical Aβ accumulation. Neocortical PET standardized uptake value ratio (SUVr) were summed and normalized to the whole cerebellum. Participants underwent spectral-domain optical coherence tomography (OCT) including blue laser autofluorescence (BAF) imaging (Heidelberg SPECTRALIS system) to identify retinal Aβ plaque inclusion bodies and measure retinal layer thickness.

Results : The values of PET SUVr, the surface area of Aβ plaque inclusion bodies, and the thickness of the inner plexiform layer (IPL) are provided in the Figures 1 and 2. There was a moderate correlation (r= 0.46, p=0.02) between PET neocortical amyloid burden and the surface area of inclusion bodies (Figure 1), and moderate correlation (r= 0.41, p=0.03) between the surface area of inclusion bodies and an increase in the thickness of the IPL – but not for other retinal neuronal layers (Figure 2).

Conclusions : The positive correlation between the surface area of inclusion bodies in the retina and amyloid aggregation in the neocortex suggests that BAF might allow for visualization of the fibrillary form of Aβ in preclinical AD subjects. The IPL is a cholinergic rich layer in the vertebrate retina³, and early cholinergic changes in preclinical disease appear to co-occur with the onset of amyloid deposit in the major cholinergic centers of the brain. ^4-6 OCT imaging of these early neuropathic changes in the retina may provide biomarkers that are both indicative of disease burden and progression and also reflective of time-specific changes in the neocortex.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

 

Aβ+ CN older adult: example of inclusion bodies around vessel walls, and in peripheral regions of the retina.