Retina pathology as a target for biomarkers for Alzheimer's disease: Current status, ophthalmopathological background, challenges, and future directions

Abstract

There is emerging evidence that amyloid beta protein (Aβ) and tau‐related lesions in the retina are associated with Alzheimer's disease (AD). Aβ and hyperphosphorylated (p)‐tau deposits have been described in the retina and were associated with small amyloid spots visualized by in vivo imaging techniques as well as degeneration of the retina. These changes correlate with brain amyloid deposition as determined by histological quantification, positron emission tomography (PET) or clinical diagnosis of AD. However, the literature is not coherent on these histopathological and in vivo imaging findings. One important reason for this is the variability in the methods and the interpretation of findings across different studies. In this perspective, we indicate the critical methodological deviations among different groups and suggest a roadmap moving forward on how to harmonize (i) histopathologic examination of retinal tissue; (ii) in vivo imaging among different methods, devices, and interpretation algorithms; and (iii) inclusion/exclusion criteria for studies aiming at retinal biomarker validation.

Choriocapillaris reduction accurately discriminates against early‐onset Alzheimer's disease

“…Moreover, a wide range of retinal microvascular and choriocapillaris changes in AD patients such as lower densities, sparser vasculature, increased tortuosity, and lower fractal dimensions have been shown in OCTA studies. 8 , 49 , 50 , 51 , 52 , 53 Here we showed that EOAD patients had lower retinal microvascular and choriocapillaris densities and sparser retinal microvascular and choriocapillaris compared to controls. These findings are in line with previous OCTA analyses.…”

OCT Imaging in Murine Models of Alzheimer’s Disease in a Systematic Review: Findings, Methodology and Future Perspectives

“…Because of the lack of standardised protocols for in vivo retinal OCT analysis in murine models of AD, analysis has recently been attempted in humans [ 85 ]; it would be necessary to determine certain recommendations for the use of retinal imaging as a potential biomarker of the disease.…”

Targeting complement C3a receptor resolves mitochondrial hyperfusion and subretinal microglial activation in progranulin-deficient frontotemporal dementia

“…This, coupled with the development of advanced non-invasive imaging technologies that can monitor retinal structure and function, makes the retina a powerful platform to interrogate neurodegenerative diseases. Indeed, retinal imaging and histopathological studies have identified changes in the retinal ganglion cell layer, retinal vasculature, and the optic nerve in patients with mild cognitive impairment and early-stage Alzheimer’s disease 57–61 . In this study, using semi-automated OCT segmentation, we observed thinning of the photoreceptor outer nuclear layer and thickening of the outer plexiform layer in GRN mutation carriers compared to healthy controls, likely indicative of photoreceptor loss and microglial expansion.…”