Retinal Biomarkers for Alzheimer Disease: The Facts and the Future

Abstract

Alzheimer disease (AD) is a significant cause of morbidity and mortality worldwide, with limited treatment options and considerable diagnostic challenges. Identification and validation of retinal changes that correlate with clinicopathologic features of AD could provide a noninvasive method of screening and monitoring progression of disease, with notable implications for developing new therapies, particularly in its preclinical stages. Retinal biomarkers that have been studied to date include structural changes in neurosensory retinal layers, alterations in vascular architecture and function, and pathologic deposition of proteins within the retina, which have all demonstrated variable correlation with the presence of preclinical or clinical AD. Evolution of specialized retinal imaging modalities and advances in artificial intelligence hold great promise for future study in this burgeoning field. The current status of research in retinal biomarkers, and some of the challenges that will need to be addressed in future work, are reviewed herein.

A model eye for fluorescent characterization of retinal cultures and tissues

“…Ocular disorders exhibit features of neurodegenerative diseases such as Alzheimer's (AD), Amyotrophic Lateral Sclerosis (ALS), and Parkinson's disease (PD), showing peculiar alterations and pathological biomarkers at the ocular level [3][4][5][6][7] . For this reason, the eye is now considered a window to the brain 8 providing a unique opportunity for the direct observation of the nervous tissue thanks to its transparency.…”

The Eye Is a Window to Systemic and Neuro-Ophthalmic Diseases

“…It may be that AI will help elucidate similar findings from the ophthalmologic examination that might predict which patients are at future risk of cognitive impairment from Alzheimer disease. As noted by Yuan and Lee 13 in this issue, retinal biomarkers may eventually be able to even screen for and monitor the progression of Alzheimer disease. Likewise, Tan et al 14 discuss, in this issue, how DL may help prognosticate systemic complications of hypertension via noninvasive retinal imaging modalities such as optical coherence tomography angiography and adaptive optics.…”

Distribution of Copper, Iron, and Zinc in the Retina, Hippocampus, and Cortex of the Transgenic APP/PS1 Mouse Model of Alzheimer’s Disease

“…A range of brain imaging modalities including computed tomography (CT) [ 15 ], magnetic resonance imaging (MRI) [ 16 , 17 ], and positron emission tomography (PET) [ 17 ] have been used to establish the presence of AD pathology. Nevertheless, they all suffer from common drawbacks, including high costs, limited accessibility, poor sensitivity, and specificity, [ 18 ] and the absence of standardization and scalability [ 19 ]. Typically, metal concentrations in anatomical regions have been measured through cutting, digestion, and analysis using various analytical techniques [ 20 ].…”

“…The eye, and specifically the retina, is an extension of the central nervous system [ 30 ]. A growing body of evidence has linked retinal changes to pathophysiological features of AD, making the eye a strategic roadmap for screening and monitoring AD progression, particularly in its preclinical stages [ 19 , 31 , 32 ]. The retina is not restricted by some of the aforementioned limitations associated with brain imaging, and thus retinal imaging offers an attractive solution when studying AD-specific biomarkers.…”