Eye test may predict Alzheimer's disease
Noninvasive retinal imaging techniques can accurately measure amyloid β (Aβ) burden in eyes and may be able to distinguish between patients with and without Alzheimer’s disease (AD), a new study has found.
“Such retinal amyloid imaging technology, capable of detecting discrete deposits at high resolution in the [central nervous system], may present a sensitive yet inexpensive tool for screening populations at risk for AD, assessing disease progression and monitoring response to therapy,” the researchers said.
Retinal flat mounts and cross-sections were created from postmortem donated eyes of 23 AD patients (mean age 78.8±2.9 years) and 14 healthy controls (mean age 76.7±3.4 years). Following staining with peroxidase- and fluorescent-based techniques, investigators found greater Aβ burden in AD eyes than in control eyes. [JCI Insight 2017;2;e93621]
In terms of Aβ morphology, retinal deposits resembled corresponding brain deposits. Control patients, for instance, showed few and diffuse Aβ deposits while AD patients had several different Aβ plaque types such as compact, classical and diffuse.
“Retinal Aβ plaques were morphologically similar to their cerebral counterparts, but their diameter was six to seven times smaller on average,” the researchers described.
“A histological examination of retinas from neuropathologically confirmed AD patients revealed certain layer and geographical distribution of Aβ deposits, especially in previously disregarded retinal regions,” they added.
For the development of a noninvasive ophthalmic imaging method to detect retinal Aβ burden, patients were given oral curcumin for either 2 or 10 days prior to retinal scanning via a scanning laser ophthalmoscope (SLO). Curcumin is a tracer commonly used for live imaging.
For the proof-of-concept clinical trial, retinal Z-stack images of 10 AD patients and six controls were obtained using an SLO. Retinal amyloid index (RAI) scores were calculated following image processing to improve signals and reduce image noise. Only spots with increased intensity were included.
Both spot number and RAI scores were significantly higher in patients with AD than in the healthy controls (p=0.0003). Moreover, Pearson’s test showed a positive linear association between RAI scores and retinal deposit number (p=0.0005). AD patients also showed a significant 2.1-fold increase in RAI scores even after controlling for age (p=0.0031).
There were no significant correlations between RAI scores and age of AD patients and Mini Mental State Examination scores.
A previous study has shown that, at least in mouse models, Aβ plaque deposits were already detectable in retina flat mounts before detection in the respective brain regions. While this indicates retinal Aβ accumulation is an early AD event, future studies are needed to establish this. [Neuroimage 2011;54;S204-S217]
“Further, the capability of the RAI score to detect AD with high sensitivity and specificity should be evaluated in follow-up studies with a greater number of cases compared with age- and sex-matched controls,” researchers said.
“Such studies could provide a better understanding of AD manifestation in the retina and further validate our methodology by determining whether retinal amyloid burden is a reliable biomarker of AD.”