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

Alzheimers Dement. 2024 Jan;20(1):728-740. doi: 10.1002/alz.13529. Epub 2023 Nov 2.

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.

Keywords: Alzheimer's disease; amyloid pathology; imaging; recruitment of clinical trials; retina; tau pathology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Biomarkers / metabolism
  • Brain / pathology
  • Humans
  • Positron-Emission Tomography / methods
  • Retina / diagnostic imaging
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • tau Proteins
  • Biomarkers