Retinal Alterations Predict Early Prodromal Signs of Neurodegenerative Disease

Int J Mol Sci. 2024 Jan 30;25(3):1689. doi: 10.3390/ijms25031689.

Abstract

Neurodegenerative diseases are an increasingly common group of diseases that occur late in life with a significant impact on personal, family, and economic life. Among these, Alzheimer's disease (AD) and Parkinson's disease (PD) are the major disorders that lead to mild to severe cognitive and physical impairment and dementia. Interestingly, those diseases may show onset of prodromal symptoms early after middle age. Commonly, the evaluation of these neurodegenerative diseases is based on the detection of biomarkers, where functional and structural magnetic resonance imaging (MRI) have shown a central role in revealing early or prodromal phases, although it can be expensive, time-consuming, and not always available. The aforementioned diseases have a common impact on the visual system due to the pathophysiological mechanisms shared between the eye and the brain. In Parkinson's disease, α-synuclein deposition in the retinal cells, as well as in dopaminergic neurons of the substantia nigra, alters the visual cortex and retinal function, resulting in modifications to the visual field. Similarly, the visual cortex is modified by the neurofibrillary tangles and neuritic amyloid β plaques typically seen in the Alzheimer's disease brain, and this may reflect the accumulation of these biomarkers in the retina during the early stages of the disease, as seen in postmortem retinas of AD patients. In this light, the ophthalmic evaluation of retinal neurodegeneration could become a cost-effective method for the early diagnosis of those diseases, overcoming the limitations of functional and structural imaging of the deep brain. This analysis is commonly used in ophthalmic practice, and interest in it has risen in recent years. This review will discuss the relationship between Alzheimer's disease and Parkinson's disease with retinal degeneration, highlighting how retinal analysis may represent a noninvasive and straightforward method for the early diagnosis of these neurodegenerative diseases.

Keywords: Alzheimer’s disease; Parkinson’s disease; RGC; amyloid plaques; dementia; dopamine; early detection; neurofibrillary tangles; prodromal symptoms; retinal degeneration; visual acuity; visual impairment.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides
  • Biomarkers
  • Humans
  • Middle Aged
  • Neurodegenerative Diseases* / diagnostic imaging
  • Neurodegenerative Diseases* / pathology
  • Parkinson Disease* / diagnostic imaging
  • Parkinson Disease* / pathology
  • Prodromal Symptoms
  • Retina / diagnostic imaging
  • Retina / pathology

Substances

  • Amyloid beta-Peptides
  • Biomarkers

Grants and funding

This manuscript was supported by local funds from the University of Ferrara, grant numbers: 2022-FAR.L-CF_004, 2023-FAR.L_medtras_CF_001, 2023-FAR.L_neuro_PA, and 2019-PRA.A-PA_001_Pignatelli. The funders had no role in the study design, data collection, analysis, decision to publish, or manuscript preparation.