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

• Published in: Alzheimer's & dementia Vol. 20; no. 1; pp. 728 - 740
• Main Authors: Alber, Jessica, Bouwman, Femke, den Haan, Jurre, Rissman, Robert A., De Groef, Lies, Koronyo‐Hamaoui, Maya, Lengyel, Imre, Thal, Dietmar Rudolf
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.01.2024; John Wiley and Sons Inc
• Subjects: Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; amyloid pathology; Biological markers; Biomarkers; Biomarkers - metabolism; Brain - pathology; Humans; imaging; Lesions; Measurement; Medical diagnosis; Medical imaging; Neurodegeneration; Pathology; Positron emission tomography; Positron-Emission Tomography - methods; recruitment of clinical trials; retina; Retina - diagnostic imaging; tau pathology; tau Proteins - metabolism; Tomography; amyloid pathology; tau pathology; recruitment of clinical trials; retina; Alzheimer's disease; imaging
• ISSN: 1552-5260; 1552-5279; 1552-5279
• DOI: 10.1002/alz.13529

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.