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Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer's disease.
Koronyo, Yosef; Biggs, David; Barron, Ernesto; Boyer, David S; Pearlman, Joel A; Au, William J; Kile, Shawn J; Blanco, Austin; Fuchs, Dieu-Trang; Ashfaq, Adeel; Frautschy, Sally; Cole, Gregory M; Miller, Carol A; Hinton, David R; Verdooner, Steven R; Black, Keith L; Koronyo-Hamaoui, Maya.
Afiliación
  • Koronyo Y; Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Biggs D; NeuroVision Imaging LLC, Sacramento, California, USA.
  • Barron E; Doheny Eye Institute, Los Angeles, California, USA.
  • Boyer DS; Retina Vitreous Associates Medical Group, Beverly Hills, California, USA.
  • Pearlman JA; Retinal Consultants Medical Group, Sacramento, California, USA.
  • Au WJ; Sutter Neuroscience Institute, Sacramento, California, USA.
  • Kile SJ; Sutter Neuroscience Institute, Sacramento, California, USA.
  • Blanco A; NeuroVision Imaging LLC, Sacramento, California, USA.
  • Fuchs DT; Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Ashfaq A; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
  • Frautschy S; Departments of Neurology and Medicine, University of California, Los Angeles, Los Angeles, California, USA; Geriatric Research Education and Clinical Center, Los Angeles, California, USA; and Veterans Greater Los Angeles Healthcare System, Los Angeles, California, USA.
  • Cole GM; Departments of Neurology and Medicine, University of California, Los Angeles, Los Angeles, California, USA; Geriatric Research Education and Clinical Center, Los Angeles, California, USA; and Veterans Greater Los Angeles Healthcare System, Los Angeles, California, USA.
  • Miller CA; Department of Pathology Program in Neuroscience, Keck School of Medicine, and.
  • Hinton DR; Departments of Pathology and Ophthalmology, USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Verdooner SR; NeuroVision Imaging LLC, Sacramento, California, USA.
  • Black KL; Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Koronyo-Hamaoui M; Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
JCI Insight ; 2(16)2017 Aug 17.
Article en En | MEDLINE | ID: mdl-28814675
ABSTRACT

BACKGROUND:

Noninvasive detection of Alzheimer's disease (AD) with high specificity and sensitivity can greatly facilitate identification of at-risk populations for earlier, more effective intervention. AD patients exhibit a myriad of retinal pathologies, including hallmark amyloid ß-protein (Aß) deposits.

METHODS:

Burden, distribution, cellular layer, and structure of retinal Aß plaques were analyzed in flat mounts and cross sections of definite AD patients and controls (n = 37). In a proof-of-concept retinal imaging trial (n = 16), amyloid probe curcumin formulation was determined and protocol was established for retinal amyloid imaging in live patients.

RESULTS:

Histological examination uncovered classical and neuritic-like Aß deposits with increased retinal Aß42 plaques (4.7-fold; P = 0.0063) and neuronal loss (P = 0.0023) in AD patients versus matched controls. Retinal Aß plaque mirrored brain pathology, especially in the primary visual cortex (P = 0.0097 to P = 0.0018; Pearson's r = 0.84-0.91). Retinal deposits often associated with blood vessels and occurred in hot spot peripheral regions of the superior quadrant and innermost retinal layers. Transmission electron microscopy revealed retinal Aß assembled into protofibrils and fibrils. Moreover, the ability to image retinal amyloid deposits with solid-lipid curcumin and a modified scanning laser ophthalmoscope was demonstrated in live patients. A fully automated calculation of the retinal amyloid index (RAI), a quantitative measure of increased curcumin fluorescence, was constructed. Analysis of RAI scores showed a 2.1-fold increase in AD patients versus controls (P = 0.0031).

CONCLUSION:

The geometric distribution and increased burden of retinal amyloid pathology in AD, together with the feasibility to noninvasively detect discrete retinal amyloid deposits in living patients, may lead to a practical approach for large-scale AD diagnosis and monitoring.

FUNDING:

National Institute on Aging award (AG044897) and The Saban and The Marciano Family Foundations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Guideline / Prognostic_studies Idioma: En Revista: JCI Insight Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Guideline / Prognostic_studies Idioma: En Revista: JCI Insight Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos