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Samuel Asanad, Michele Fantini, William Charles Sultan, Marco Nassisi, Christian Felix, Jessica Wu, Rustum Karanjia, Fred N. Ross-Cisneros, Michael Harrington, Alfredo A Sadun; The Retina in Preclinical Alzheimer’s Disease: Degeneration of the Eye Before the Brain. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5946.
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© ARVO (1962-2015); The Authors (2016-present)
Preclinical Alzheimer’s disease (AD) describes individuals with AD pathology who are cognitively healthy. We have shown that preclinical AD can be detected more sensitively and specifically by the beta amyloid 42 (Aß42)/Tau ratio relative to the concentration of these cerebrospinal fluid (CSF) markers independently (Harrington et al 2013). The purpose of this study was to investigate retinal thickness changes in asymptomatic AD in correlation with the Aß42/Tau ratio.
For this prospective study, 27 eyes from 27 pre-clinical AD participants (mean age: 75.2 ± 8.4 years) were compared to 17 eyes from 17 age-matched controls (mean age: 74.1 ± 7.9 years; p=0.5). Spectral-Domain OCT scans were acquired for the retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GC-IPL), and the full macular thickness, comprising all retina layers. The thicknesses of these 3 regions were measured and compared between the two cohorts and correlated with their CSF levels of Aß42, Tau, and Aß42/Tau ratio. Analysis of Covariance was used for statistical analysis.
The RNFL was significantly thinner in AD relative to controls (10.2 ± 2.4 mm; p<0.001). Thinning was greatest superiorly (5.7 ± 1.42 mm, p=0.07) relative to nasal, inferior, and temporal quadrants. The GC-IPL and full macular thickness were also thinner in AD relative to controls (1.3 ± 0.85 mm and 2.4 ± 0.49 mm, respectively) although not statistically significant (p>0.05). Relative to Aß42 and Tau alone, the Aß42/Tau ratio correlated the strongest with thickness for all 3 regions, although statistically significant particularly for the RNFL (p<0.004).
These findings illustrate early pathological manifestations of AD at the retinal level, preceding cognitive deficits. We demonstrate the diagnostic and predictive value of the Aß42/Tau ratio for these retinal changes relative to the concentrations of these CSF markers alone. Intriguingly, our findings in preclinical AD resembled those in late-stage AD, whereby thinning was greatest superiorly. Such precise objective and quantitative measurements in early disease may be useful in providing an enhanced, non-invasive means of assessing AD.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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