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Ocular indicators of Alzheimer's: exploring disease in the retina.
Acta Neuropathol. 2016 12; 132(6):767-787.AN

Abstract

Although historically perceived as a disorder confined to the brain, our understanding of Alzheimer's disease (AD) has expanded to include extra-cerebral manifestation, with mounting evidence of abnormalities in the eye. Among ocular tissues, the retina, a developmental outgrowth of the brain, is marked by an array of pathologies in patients suffering from AD, including nerve fiber layer thinning, degeneration of retinal ganglion cells, and changes to vascular parameters. While the hallmark pathological signs of AD, amyloid β-protein (Aβ) plaques and neurofibrillary tangles (NFT) comprising hyperphosphorylated tau (pTau) protein, have long been described in the brain, identification of these characteristic biomarkers in the retina has only recently been reported. In particular, Aβ deposits were discovered in post-mortem retinas of advanced and early stage cases of AD, in stark contrast to non-AD controls. Subsequent studies have reported elevated Aβ42/40 peptides, morphologically diverse Aβ plaques, and pTau in the retina. In line with the above findings, animal model studies have reported retinal Aβ deposits and tauopathy, often correlated with local inflammation, retinal ganglion cell degeneration, and functional deficits. This review highlights the converging evidence that AD manifests in the eye, especially in the retina, which can be imaged directly and non-invasively. Visual dysfunction in AD patients, traditionally attributed to well-documented cerebral pathology, can now be reexamined as a direct outcome of retinal abnormalities. As we continue to study the disease in the brain, the emerging field of ocular AD warrants further investigation of how the retina may faithfully reflect the neurological disease. Indeed, detection of retinal AD pathology, particularly the early presenting amyloid biomarkers, using advanced high-resolution imaging techniques may allow large-scale screening and monitoring of at-risk populations.

Authors+Show Affiliations

Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Los Angeles, 90048, CA, USA.Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Los Angeles, 90048, CA, USA.Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Los Angeles, 90048, CA, USA.Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Los Angeles, 90048, CA, USA. maya.koronyo@cshs.org. Department of Biomedical Sciences, Cedars-Sinai Medical Center, 110 George Burns Rd., Los Angeles, CA, 90048, USA. maya.koronyo@cshs.org.

Pub Type(s)

Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27645291

Citation

Hart, Nadav J., et al. "Ocular Indicators of Alzheimer's: Exploring Disease in the Retina." Acta Neuropathologica, vol. 132, no. 6, 2016, pp. 767-787.
Hart NJ, Koronyo Y, Black KL, et al. Ocular indicators of Alzheimer's: exploring disease in the retina. Acta Neuropathol. 2016;132(6):767-787.
Hart, N. J., Koronyo, Y., Black, K. L., & Koronyo-Hamaoui, M. (2016). Ocular indicators of Alzheimer's: exploring disease in the retina. Acta Neuropathologica, 132(6), 767-787.
Hart NJ, et al. Ocular Indicators of Alzheimer's: Exploring Disease in the Retina. Acta Neuropathol. 2016;132(6):767-787. PubMed PMID: 27645291.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ocular indicators of Alzheimer's: exploring disease in the retina. AU - Hart,Nadav J, AU - Koronyo,Yosef, AU - Black,Keith L, AU - Koronyo-Hamaoui,Maya, Y1 - 2016/09/19/ PY - 2016/06/17/received PY - 2016/09/01/accepted PY - 2016/08/29/revised PY - 2016/9/21/pubmed PY - 2017/9/21/medline PY - 2016/9/21/entrez KW - Alzheimer’s disease KW - Amyloid-beta KW - Neurodegenerative disease KW - Ocular abnormalities KW - Retinal biomarkers KW - Tauopathy SP - 767 EP - 787 JF - Acta neuropathologica JO - Acta Neuropathol VL - 132 IS - 6 N2 - Although historically perceived as a disorder confined to the brain, our understanding of Alzheimer's disease (AD) has expanded to include extra-cerebral manifestation, with mounting evidence of abnormalities in the eye. Among ocular tissues, the retina, a developmental outgrowth of the brain, is marked by an array of pathologies in patients suffering from AD, including nerve fiber layer thinning, degeneration of retinal ganglion cells, and changes to vascular parameters. While the hallmark pathological signs of AD, amyloid β-protein (Aβ) plaques and neurofibrillary tangles (NFT) comprising hyperphosphorylated tau (pTau) protein, have long been described in the brain, identification of these characteristic biomarkers in the retina has only recently been reported. In particular, Aβ deposits were discovered in post-mortem retinas of advanced and early stage cases of AD, in stark contrast to non-AD controls. Subsequent studies have reported elevated Aβ42/40 peptides, morphologically diverse Aβ plaques, and pTau in the retina. In line with the above findings, animal model studies have reported retinal Aβ deposits and tauopathy, often correlated with local inflammation, retinal ganglion cell degeneration, and functional deficits. This review highlights the converging evidence that AD manifests in the eye, especially in the retina, which can be imaged directly and non-invasively. Visual dysfunction in AD patients, traditionally attributed to well-documented cerebral pathology, can now be reexamined as a direct outcome of retinal abnormalities. As we continue to study the disease in the brain, the emerging field of ocular AD warrants further investigation of how the retina may faithfully reflect the neurological disease. Indeed, detection of retinal AD pathology, particularly the early presenting amyloid biomarkers, using advanced high-resolution imaging techniques may allow large-scale screening and monitoring of at-risk populations. SN - 1432-0533 UR - https://www.unboundmedicine.com/medline/citation/27645291/Ocular_indicators_of_Alzheimer's:_exploring_disease_in_the_retina_ L2 - https://dx.doi.org/10.1007/s00401-016-1613-6 DB - PRIME DP - Unbound Medicine ER -