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Retinal pathological features and proteome signatures of Alzheimer's disease.
Koronyo, Yosef; Rentsendorj, Altan; Mirzaei, Nazanin; Regis, Giovanna C; Sheyn, Julia; Shi, Haoshen; Barron, Ernesto; Cook-Wiens, Galen; Rodriguez, Anthony R; Medeiros, Rodrigo; Paulo, Joao A; Gupta, Veer B; Kramerov, Andrei A; Ljubimov, Alexander V; Van Eyk, Jennifer E; Graham, Stuart L; Gupta, Vivek K; Ringman, John M; Hinton, David R; Miller, Carol A; Black, Keith L; Cattaneo, Antonino; Meli, Giovanni; Mirzaei, Mehdi; Fuchs, Dieu-Trang; Koronyo-Hamaoui, Maya.
Affiliation
  • Koronyo Y; Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Los Angeles, CA, 90048, USA.
  • Rentsendorj A; Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Los Angeles, CA, 90048, USA.
  • Mirzaei N; Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Los Angeles, CA, 90048, USA.
  • Regis GC; Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Los Angeles, CA, 90048, USA.
  • Sheyn J; Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Los Angeles, CA, 90048, USA.
  • Shi H; Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Los Angeles, CA, 90048, USA.
  • Barron E; Doheny Eye Institute, University of California Los Angeles, Los Angeles, CA, USA.
  • Cook-Wiens G; Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
  • Rodriguez AR; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Medeiros R; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
  • Paulo JA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
  • Gupta VB; Department of Cell Biology, Harvard Medical School, Boston, USA.
  • Kramerov AA; School of Medicine, Deakin University, Victoria, Australia.
  • Ljubimov AV; Department of Biomedical Sciences and Eye Program, Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Van Eyk JE; Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Los Angeles, CA, 90048, USA.
  • Graham SL; Department of Biomedical Sciences and Eye Program, Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Gupta VK; Departments of Neurology and Biomedical Sciences, Division of Applied Cell Biology and Physiology, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Los Angeles, CA, USA.
  • Ringman JM; Departments of Neurology and Biomedical Sciences, Division of Applied Cell Biology and Physiology, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd., Los Angeles, CA, USA.
  • Hinton DR; Barbra Streisand Women's Heart Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Miller CA; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Black KL; Save Sight Institute, University of Sydney, Sydney, NSW, Australia.
  • Cattaneo A; Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
  • Meli G; Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
  • Mirzaei M; Department of Neurology, Keck School of Medicine of USC, Los Angeles, CA, USA.
  • Fuchs DT; Departments of Pathology and Ophthalmology, Keck School of Medicine, USC Roski Eye Institute, University of Southern California, Los Angeles, CA, USA.
  • Koronyo-Hamaoui M; Department of Pathology Program in Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Acta Neuropathol ; 145(4): 409-438, 2023 04.
Article in En | MEDLINE | ID: mdl-36773106
Alzheimer's disease (AD) pathologies were discovered in the accessible neurosensory retina. However, their exact nature and topographical distribution, particularly in the early stages of functional impairment, and how they relate to disease progression in the brain remain largely unknown. To better understand the pathological features of AD in the retina, we conducted an extensive histopathological and biochemical investigation of postmortem retina and brain tissues from 86 human donors. Quantitative examination of superior and inferior temporal retinas from mild cognitive impairment (MCI) and AD patients compared to those with normal cognition (NC) revealed significant increases in amyloid ß-protein (Aß42) forms and novel intraneuronal Aß oligomers (AßOi), which were closely associated with exacerbated retinal macrogliosis, microgliosis, and tissue atrophy. These pathologies were unevenly distributed across retinal layers and geometrical areas, with the inner layers and peripheral subregions exhibiting most pronounced accumulations in the MCI and AD versus NC retinas. While microgliosis was increased in the retina of these patients, the proportion of microglial cells engaging in Aß uptake was reduced. Female AD patients exhibited higher levels of retinal microgliosis than males. Notably, retinal Aß42, S100 calcium-binding protein B+ macrogliosis, and atrophy correlated with severity of brain Aß pathology, tauopathy, and atrophy, and most retinal pathologies reflected Braak staging. All retinal biomarkers correlated with the cognitive scores, with retinal Aß42, far-peripheral AßOi and microgliosis displaying the strongest correlations. Proteomic analysis of AD retinas revealed activation of specific inflammatory and neurodegenerative processes and inhibition of oxidative phosphorylation/mitochondrial, and photoreceptor-related pathways. This study identifies and maps retinopathy in MCI and AD patients, demonstrating the quantitative relationship with brain pathology and cognition, and may lead to reliable retinal biomarkers for noninvasive retinal screening and monitoring of AD.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alzheimer Disease Type of study: Prognostic_studies Limits: Female / Humans / Male Language: En Journal: Acta Neuropathol Year: 2023 Document type: Article Affiliation country: Estados Unidos Country of publication: Alemania
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Alzheimer Disease Type of study: Prognostic_studies Limits: Female / Humans / Male Language: En Journal: Acta Neuropathol Year: 2023 Document type: Article Affiliation country: Estados Unidos Country of publication: Alemania