Shi H, Koronyo Y, Rentsendorj A, Regis GC, Sheyn J, Fuchs DT, Kramerov AA, Ljubimov AV, Dumitrascu OM, Rodriguez AR, Barron E, Hinton DR, Black KL, Miller CA, Mirzaei N, Koronyo-Hamaoui M. Identification of early pericyte loss and vascular amyloidosis in Alzheimer's disease retina. Acta Neuropathol. 2020 May;139(5):813-836. Epub 2020 Feb 10 PubMed.
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UCSC
Early diagnosis of Alzheimer's disease remains a major unmet need. In this insightful study, Dr. Koronyo-Hamaoui and co-workers from the Cedars-Sinai Medical Center report that early pathophysiological changes associated with Alzheimer's include a deficiency in retinal platelet-derived growth factor receptor β (PDGFRβ) and pericyte loss, especially in retinal capillaries. This may affect blood flow and blood-retinal barrier integrity. The authors find these changes to be associated with significant buildup of Aβ deposits within retinal vasculature, which was also found to be predictive of the cerebral amyloid angiopathy severity.
The study examined an impressively sized cohort of 62 postmortem donor eyes at a remarkable level of detail. Donors included mild cognitively impaired (MCI) and Alzheimer's patients at different stages of disease progression, as well as cognitively normal individuals. The study showed that clinically more severe Alzheimer’s was correlated with a higher degree of blood-retinal-barrier breakdown, with greater PDGFRβ deficiency and pericyte loss, and amyloid deposit in retinal vessel walls.
Early stage Alzheimer's patients (MCI) could be distinguished from non-demented reference group. This is particularly important, as it shows that this finding can lead to novel approaches that can be used to detect the disease noninvasively at early stages. Furthermore, the identified deficiency in platelet-derived growth factor receptor β signaling represents a well-defined target for future development of molecular therapeutics.
References:
Shi H, Koronyo Y, Rentsendorj A, Regis GC, Sheyn J, Fuchs DT, Kramerov AA, Ljubimov AV, Dumitrascu OM, Rodriguez AR, Barron E, Hinton DR, Black KL, Miller CA, Mirzaei N, Koronyo-Hamaoui M. Identification of early pericyte loss and vascular amyloidosis in Alzheimer's disease retina. Acta Neuropathol. 2020 May;139(5):813-836. Epub 2020 Feb 10 PubMed.
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