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Amyloid Beta Immunoreactivity in the Retinal Ganglion Cell Layer of the Alzheimer's Eye.
Front Neurosci. 2020; 14:758.FN

Abstract

Alzheimer's disease (AD) is the most prevalent form of dementia, accounting for 60-70% of all dementias. AD is often under-diagnosed and recognized only at a later, more advanced stage, and this delay in diagnosis has been suggested as a contributing factor in the numerous unsuccessful AD treatment trials. Although there is no known cure for AD, early diagnosis is important for disease management and care. A hallmark of AD is the deposition of amyloid-β (Aβ)-containing senile neuritic plaques and neurofibrillary tangles composed of hyperphosporylated tau in the brain. However, current in vivo methods to quantify Aβ in the brain are invasive, requiring radioactive tracers and positron emission tomography. Toward development of alternative methods to assess AD progression, we focus on the retinal manifestation of AD pathology. The retina is an extension of the central nervous system uniquely accessible to light-based, non-invasive ophthalmic imaging. However, earlier studies in human retina indicate that the literature is divided on the presence of Aβ in the AD retina. To help resolve this disparity, this study assessed retinal tissues from neuropathologically confirmed AD cases to determine the regional distribution of Aβ in retinal wholemounts and to inform on future retinal image studies targeting Aβ. Concurrent post-mortem brain tissues were also collected. Neuropathological cortical assessments including neuritic plaque (NP) scores and cerebral amyloid angiopathy (CAA) were correlated with retinal Aβ using immunohistochemistry, confocal microscopy, and quantitative image analysis. Aβ load was compared between AD and control (non-AD) eyes. Our results indicate that levels of intracellular and extracellular Aβ retinal deposits were significantly higher in AD than controls. Mid-peripheral Aβ levels were greater than central retina in both AD and control eyes. In AD retina, higher intracellular Aβ was associated with lower NP score, while higher extracellular Aβ was associated with higher CAA score. Our data support the feasibility of using the retinal tissue to assess ocular Aβ as a surrogate measure of Aβ in the brain of individuals with AD. Specifically, mid-peripheral retina possesses more Aβ deposition than central retina, and thus may be the optimal location for future in vivo ocular imaging.

Authors+Show Affiliations

Department of Ophthalmology and Visual Sciences, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada. School of Engineering Science, Simon Fraser University, Burnaby, BC, Canada.Department of Surgery, Division of Ophthalmology, University of Calgary, Calgary, AB, Canada.Department of Family Medicine, Queen's University, Kingston, ON, Canada.Department of Ophthalmology and Visual Sciences, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada.Department of Ophthalmology and Visual Sciences, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada.Department of Pathology, Vancouver General Hospital, The University of British Columbia, Vancouver, BC, Canada.Department of Pathology, Vancouver General Hospital, The University of British Columbia, Vancouver, BC, Canada.Division of Neurology, Department of Medicine, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada.Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, NS, Canada.School of Engineering Science, Simon Fraser University, Burnaby, BC, Canada.School of Engineering Science, Simon Fraser University, Burnaby, BC, Canada.Department of Ophthalmology and Visual Sciences, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada.Department of Ophthalmology and Visual Sciences, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32848548

Citation

Lee, Sieun, et al. "Amyloid Beta Immunoreactivity in the Retinal Ganglion Cell Layer of the Alzheimer's Eye." Frontiers in Neuroscience, vol. 14, 2020, p. 758.
Lee S, Jiang K, McIlmoyle B, et al. Amyloid Beta Immunoreactivity in the Retinal Ganglion Cell Layer of the Alzheimer's Eye. Front Neurosci. 2020;14:758.
Lee, S., Jiang, K., McIlmoyle, B., To, E., Xu, Q. A., Hirsch-Reinshagen, V., Mackenzie, I. R., Hsiung, G. R., Eadie, B. D., Sarunic, M. V., Beg, M. F., Cui, J. Z., & Matsubara, J. A. (2020). Amyloid Beta Immunoreactivity in the Retinal Ganglion Cell Layer of the Alzheimer's Eye. Frontiers in Neuroscience, 14, 758. https://doi.org/10.3389/fnins.2020.00758
Lee S, et al. Amyloid Beta Immunoreactivity in the Retinal Ganglion Cell Layer of the Alzheimer's Eye. Front Neurosci. 2020;14:758. PubMed PMID: 32848548.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amyloid Beta Immunoreactivity in the Retinal Ganglion Cell Layer of the Alzheimer's Eye. AU - Lee,Sieun, AU - Jiang,Kailun, AU - McIlmoyle,Brandon, AU - To,Eleanor, AU - Xu,Qinyuan Alis, AU - Hirsch-Reinshagen,Veronica, AU - Mackenzie,Ian R, AU - Hsiung,Ging-Yuek R, AU - Eadie,Brennan D, AU - Sarunic,Marinko V, AU - Beg,Mirza Faisal, AU - Cui,Jing Z, AU - Matsubara,Joanne A, Y1 - 2020/07/31/ PY - 2020/05/12/received PY - 2020/06/29/accepted PY - 2020/8/28/entrez PY - 2020/8/28/pubmed PY - 2020/8/28/medline KW - Alzheimer’s disease KW - Neuritic plaques KW - Temporal retina KW - amyloid-beta KW - mid-peripheral retina KW - ophthalmic imaging KW - retina KW - retinal ganglion cell SP - 758 EP - 758 JF - Frontiers in neuroscience JO - Front Neurosci VL - 14 N2 - Alzheimer's disease (AD) is the most prevalent form of dementia, accounting for 60-70% of all dementias. AD is often under-diagnosed and recognized only at a later, more advanced stage, and this delay in diagnosis has been suggested as a contributing factor in the numerous unsuccessful AD treatment trials. Although there is no known cure for AD, early diagnosis is important for disease management and care. A hallmark of AD is the deposition of amyloid-β (Aβ)-containing senile neuritic plaques and neurofibrillary tangles composed of hyperphosporylated tau in the brain. However, current in vivo methods to quantify Aβ in the brain are invasive, requiring radioactive tracers and positron emission tomography. Toward development of alternative methods to assess AD progression, we focus on the retinal manifestation of AD pathology. The retina is an extension of the central nervous system uniquely accessible to light-based, non-invasive ophthalmic imaging. However, earlier studies in human retina indicate that the literature is divided on the presence of Aβ in the AD retina. To help resolve this disparity, this study assessed retinal tissues from neuropathologically confirmed AD cases to determine the regional distribution of Aβ in retinal wholemounts and to inform on future retinal image studies targeting Aβ. Concurrent post-mortem brain tissues were also collected. Neuropathological cortical assessments including neuritic plaque (NP) scores and cerebral amyloid angiopathy (CAA) were correlated with retinal Aβ using immunohistochemistry, confocal microscopy, and quantitative image analysis. Aβ load was compared between AD and control (non-AD) eyes. Our results indicate that levels of intracellular and extracellular Aβ retinal deposits were significantly higher in AD than controls. Mid-peripheral Aβ levels were greater than central retina in both AD and control eyes. In AD retina, higher intracellular Aβ was associated with lower NP score, while higher extracellular Aβ was associated with higher CAA score. Our data support the feasibility of using the retinal tissue to assess ocular Aβ as a surrogate measure of Aβ in the brain of individuals with AD. Specifically, mid-peripheral retina possesses more Aβ deposition than central retina, and thus may be the optimal location for future in vivo ocular imaging. SN - 1662-4548 UR - https://www.unboundmedicine.com/medline/citation/32848548/Amyloid_Beta_Immunoreactivity_in_the_Retinal_Ganglion_Cell_Layer_of_the_Alzheimer's_Eye_ L2 - https://doi.org/10.3389/fnins.2020.00758 DB - PRIME DP - Unbound Medicine ER -
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