Phosphorylated α‐synuclein in the retina is a biomarker of Parkinson's disease pathology severity

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Title: Phosphorylated α‐synuclein in the retina is a biomarker of Parkinson's disease pathology severity
Authors: Ortuño Lizarán, Isabel | Beach, Thomas G. | Serrano, Geidy | Walker, Douglas G. | Adler, Charles H. | Cuenca, Nicolás
Research Group/s: Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS)
Center, Department or Service: Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología
Keywords: Parkinson’s disease | Human | Retina | Phosphorylated α-synuclein | Vision
Knowledge Area: Fisiología | Biología Celular
Issue Date: Aug-2018
Publisher: Wiley
Citation: Movement Disorders. 2018, 33(8): 1315-1324. doi:10.1002/mds.27392
Abstract: Background: PD patients often have visual alterations, for example, loss of visual acuity, contrast sensitivity or motion perception, and diminished electroretinogram responses. PD pathology is mainly characterized by the accumulation of pathological α‐synuclein deposits in the brain, but little is known about how synucleinopathy affects the retina. Objective: To study the correlation between α‐synuclein deposits in the retina and brain of autopsied subjects with PD and incidental Lewy body disease. Methods: We evaluated the presence of phosphorylated α‐synuclein in the retina of autopsied subjects with PD (9 subjects), incidental Lewy body disease (4 subjects), and controls (6 subjects) by immunohistochemistry and compared the retinal synucleinopathy with brain disease severity indicators. Results: Whereas controls did not show any phosphorylated α‐synuclein immunoreactivity in their retina, all PD subjects and 3 of 4 incidental Lewy body disease subjects had phosphorylated α‐synuclein deposits in ganglion cell perikarya, dendrites, and axons, some of them resembling brain Lewy bodies and Lewy neurites. The Lewy‐type synucleinopathy density in the retina significantly correlated with Lewy‐type synucleinopathy density in the brain, with the Unified Parkinson's disease pathology stage and with the motor UPDRS. Conclusion: These data suggest that phosphorylated α‐synuclein accumulates in the retina in parallel with that in the brain, including in early stages preceding development of clinical signs of parkinsonism or dementia. Therefore, the retina may provide an in vivo indicator of brain pathology severity, and its detection could help in the diagnosis and monitoring of disease progression.
Sponsor: This work was supported by the Michael J. Fox Foundation for Parkinson's Research. I.O.L. acknowledges financial support from the Ministerio de Educación, Spain (FPU 14/03166). N.C. acknowledges financial support from the Ministerio de Economía y Competitividad, Spain (MINECO‐FEDER‐BFU2015‐67139‐R), Generalitat Valenciana (Prometeo 2016/158), and Instituto Carlos III (ISCIII RETICS‐FEDER RD12/0034/0010). The Brain and Body Donation Program has been supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026), the National Institute on Aging (P30 AG19610), the Arizona Department of Health Services, the Arizona Biomedical Research Commission, and the Michael J. Fox Foundation for Parkinson's Research.
ISSN: 0885-3185 (Print) | 1531-8257 (Online)
DOI: 10.1002/mds.27392
Language: eng
Type: info:eu-repo/semantics/article
Rights: © 2018 International Parkinson and Movement Disorder Society
Peer Review: si
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Appears in Collections:INV - NEUROVIS - Artículos de Revistas

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