Alzheimer's disease pathophysiology in the Retina

Bhakta Prasad Gaire; Yosef Koronyo; Dieu-Trang Fuchs; Haoshen Shi; Altan Rentsendorj; Ron Danziger; Jean-Philippe Vit; Nazanin Mirzaei; Jonah Doustar; Julia Sheyn; Harald Hampel; Andrea Vergallo; Miyah R Davis; Ousman Jallow; Filippo Baldacci; Steven R Verdooner; Ernesto Barron; Mehdi Mirzaei; Vivek K Gupta; Stuart L Graham; Mourad Tayebi; Roxana O Carare; Alfredo A Sadun; Carol A Miller; Oana M Dumitrascu; Shouri Lahiri; Liang Gao; Keith L Black; Maya Koronyo-Hamaoui

doi:10.1016/j.preteyeres.2024.101273

Alzheimer's disease pathophysiology in the Retina

Prog Retin Eye Res. 2024 May 15:101:101273. doi: 10.1016/j.preteyeres.2024.101273. Online ahead of print.

Authors

Bhakta Prasad Gaire¹, Yosef Koronyo¹, Dieu-Trang Fuchs¹, Haoshen Shi¹, Altan Rentsendorj¹, Ron Danziger², Jean-Philippe Vit¹, Nazanin Mirzaei¹, Jonah Doustar¹, Julia Sheyn¹, Harald Hampel³, Andrea Vergallo³, Miyah R Davis¹, Ousman Jallow¹, Filippo Baldacci⁴, Steven R Verdooner⁵, Ernesto Barron⁶, Mehdi Mirzaei⁷, Vivek K Gupta⁷, Stuart L Graham⁸, Mourad Tayebi⁹, Roxana O Carare¹⁰, Alfredo A Sadun⁶, Carol A Miller¹¹, Oana M Dumitrascu¹², Shouri Lahiri², Liang Gao¹³, Keith L Black¹, Maya Koronyo-Hamaoui¹⁴

Affiliations

¹ Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
² Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
³ Sorbonne University, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France.
⁴ Sorbonne University, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France; Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy.
⁵ NeuroVision Imaging Inc., Sacramento, CA, USA.
⁶ Department of Ophthalmology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA; Doheny Eye Institute, Los Angeles, CA, USA.
⁷ Department of Clinical Medicine, Health and Human Sciences, Macquarie Medical School, Macquarie University, Sydney, NSW, Australia.
⁸ Department of Clinical Medicine, Health and Human Sciences, Macquarie Medical School, Macquarie University, Sydney, NSW, Australia; Department of Clinical Medicine, Macquarie University, Sydney, NSW, Australia.
⁹ School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.
¹⁰ Department of Clinical Neuroanatomy, University of Southampton, Southampton, UK.
¹¹ Department of Pathology Program in Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹² Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA.
¹³ Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.
¹⁴ Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences, Division of Applied Cell Biology and Physiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address: maya.koronyo@csmc.edu.

PMID: 38759947
DOI: 10.1016/j.preteyeres.2024.101273

Abstract

The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks of AD, including amyloid β-protein (Aβ) deposits and abnormal tau protein isoforms, in the retinas of AD patients and animal models. Moreover, structural and functional vascular abnormalities such as reduced blood flow, vascular Aβ deposition, and blood-retinal barrier damage, along with inflammation and neurodegeneration, have been described in retinas of patients with mild cognitive impairment and AD dementia. Histological, biochemical, and clinical studies have demonstrated that the nature and severity of AD pathologies in the retina and brain correspond. Proteomics analysis revealed a similar pattern of dysregulated proteins and biological pathways in the retina and brain of AD patients, with enhanced inflammatory and neurodegenerative processes, impaired oxidative-phosphorylation, and mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific amyloid deposits, as well as vasculopathy and neurodegeneration in the retina of living AD patients, suggesting alterations at different disease stages and links to brain pathology. Current and exploratory ophthalmic imaging modalities, such as optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, and hyperspectral imaging, may offer promise in the clinical assessment of AD. However, further research is needed to deepen our understanding of AD's impact on the retina and its progression. To advance this field, future studies require replication in larger and diverse cohorts with confirmed AD biomarkers and standardized retinal imaging techniques. This will validate potential retinal biomarkers for AD, aiding in early screening and monitoring.

Keywords: Alzheimer's disease; Inflammation; Neurodegenerative diseases; Retinal imaging; Retinal vascular pathology; Visual impairments.

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Abstract

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