• Retinal Scanning May Help Detect Alzheimer Disease in Living Patients

    Written By: Lynda Seminara
    Selected By: Deepak P. Edward, MD

    Journal Highlights

    JCI Insight
    2017;2(16):e93621

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    Retinal examination may be a nonin­vasive method of detecting Alzheimer disease (AD). The retinas of deceased patients with AD exhibit myriad retinal pathologies, including the hallmark amyloid-β (Aβ) protein. Koronyo et al., in a proof-of-concept study, demon­strated that such evidence also exists in the retinas of living patients. According to the retinal amyloid index (RAI) developed by the investigators, index scores were more than twice as high for patients with AD than in cognitively normal controls.

    The authors first examined the burden, distribution, cellular layer, and structure of retinal Aβ plaques in do­nor tissue (eyes and brain) of patients with definitive AD (n = 23) and cog­nitively normal controls (n = 14). An amyloid probe curcumin formulation was derived from histologic findings, and a protocol for retinal amyloid imaging was established and applied to living patients (10 with AD, 6 healthy controls).

    Histologic examination showed that patients with AD had classic and neu­ritic-like Aβ deposits, with increased retinal Aβ42 plaques (4.7-fold; p = .0063) and neuronal loss (p = .0023) relative to matched controls. The retinal Aβ plaque presentation mirrored brain pathology, particularly in the primary visual cortex. Retinal deposits often were associated with blood vessels and occurred in hot-spot peripheral regions of the superior quadrant and inner­most layer of the retina. Transmission electron microscopy showed the assem­blage of retinal Aβ into protofibrils and fibrils.

    The authors then demonstrated the ability to image retinal amyloid deposits with solid-lipid curcumin and a mod­ified scanning laser ophthalmoscope in living patients. A fully automated calculation of the RAI, a quantitative measure of increased curcumin fluo­rescence, was devised. Analysis of RAI scores showed that scores for patients with AD were 2.1 times higher than those of controls.

    The geometric distribution and increased burden of retinal amyloid pathology in AD, coupled with the fea­sibility to noninvasively detect retinal amyloid deposits in living patients, may lead to a practical approach for large-scale diagnosis and monitoring of AD. Such imaging technology may prove to be sensitive and inexpensive for screen­ing people at risk for AD.

    The original article can be found here.