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Ocular amyloid imaging at the crossroad of Alzheimer’s disease and age-related macular degeneration: implications for diagnosis and therapy

  • Sally S. Ong
  • Alan D. Proia
  • Heather E. Whitson
  • Sina Farsiu
  • P. Murali Doraiswamy
  • Eleonora M. LadEmail author
Review

Abstract

Alzheimer’s disease (AD) and age-related macular degeneration (AMD) are important disorders of aging, but significant challenges remain in diagnosis and therapy. Amyloid-beta (Aβ), found in the brain and a defining feature of AD, has also been observed in the retina in both AD and AMD. While current diagnostic modalities for detecting Aβ in the brain are costly or invasive, Aβ in the retina can be noninvasively and conveniently imaged using modern photonic imaging systems such as optical coherence tomography (OCT). Moreover, since many of these retinal changes occur before degenerative changes can be detected in the brain, ocular amyloid biomarkers could be utilized to detect AD as well as AMD in their earliest stages when therapy may be most effective in halting disease progression. Novel technologies to quantify retinal biomarkers have the potential to facilitate early diagnosis and noninvasive monitoring of disease progression with important therapeutic implications.

Keywords

Alzheimer’s disease Amyloid beta Optical coherence tomography Retinal imaging 

Abbreviations

Amyloid-beta

AD

Alzheimer’s disease

AMD

Age-related macular degeneration

aMCI

Amnestic mild cognitive impairment

APP

Amyloid precursor protein

ARIA-E

Amyloid-related imaging abnormalities-edema

BEAM

Brain–eye amyloid memory study

CSF

Cerebrospinal fluid

ERG

Electroretinogram

FAF

Fundus autofluorescence

GC-IPL

Ganglion cell-inner plexiform layer

MCI

Mild cognitive impairment

MRI

Magnetic resonance imaging

NFT

Neurofibrillary tau

OCT

Optical coherence tomography

PET

Positron emission tomography

RNFL

Retinal nerve fiber layer

RPE

Retinal pigment epithelium

VEP

Visual evoked potential

Notes

Acknowledgements

EML had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. No funding organization or sponsor had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The authors gratefully thank Michael Kelly for assistance with acquisition of images and preparation of figures.

Author contributions

SSO and EML outlined the manuscript and designed figures, SSO wrote the initial draft, SSO and EML performed the literature search, and EML, PMD, SF, HEW and ADP provided crucial edits, revisions, and comments. SF supplied expertise on imaging; EML, PMD, HEW and ADP added expertise on clinical applications; and SSO, EML and PMD provided final edits.

Compliance with ethical standards

Conflicts of interest

SSO receives research funding from the International Retinal Research Foundation. EML has received research grants from Alzheimer’s Association, Duke Institute for Brain Sciences and the National Eye Institute. HEW has received research grants from the Veterans Affairs Medical Center, National Institute on Aging and Alzheimer’s Association. SF has received research grants from the National Institute of Health and Duke University, and holds US patent 8811745 and 9299155. PMD has received advisory fees from Avid/Lilly, Anthrotronix, Muses Labs, AstraZeneca, Cognoptix, Lundbeck/Takeda, Piramal, Genomind, Sonexa, Targacept, NeuroPro, Neurocog Trials, Forum, Holmusk, and T3D Therapeutics; research grants (through Duke University) from Elan, Avid/Lilly, Avanir, Neuronetrix, Forum, Alzheimer’s Drug Discovery Foundation, USC, and ADCS/UCSD; fees for lectures from Hintsa Performance, Crossings; and fees for developing educational materials from Physicians Postgraduate Press. PMD owns shares or options in Maxwell Health, Muses Labs, Anthrotronix, Evidation, and Adverse Events Inc (whose products are not discussed here), and has received travel funds from Pfizer and the World Economic Forum. ADP reports no competing interests.

Ethical standards

This articles does not contain any studies with human participants performed by any of the authors.

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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of OphthalmologyDuke University Medical CenterDurhamUSA
  2. 2.Department of PathologyDuke University Medical CenterDurhamUSA
  3. 3.Department of MedicineDuke University Medical CenterDurhamUSA
  4. 4.Department of Biomedical EngineeringDuke University Medical CenterDurhamUSA
  5. 5.Division of Translational Neuroscience, Department of PsychiatryDuke University Medical CenterDurhamUSA

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