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Frank Corapi, Melanie C W Campbell, Laura Emptage, Rachel Redekop, Monika Kitor, Veronica Hirsch-Reinshagen, Robin Hsiung, Ian Mackenzie; Correlation between amyloid beta deposits in ex vivo retinas and severity of Alzheimer’s brain pathology. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1582. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Alzheimer’s disease (AD) is a neurodegenerative disease and has characteristic deposition of amyloid-beta (Aβ) in the brain. Aβ has been detected in the neural retina which is optically accessible. We have previously reported a correlation between the severity of diagnosis based on brain tissue and the number of deposits in the retina. Here, the ex vivo Aβ pathology of the eye and brain are further compared with additional tissues.
Eyes and brains were obtained from donors with a variety of neurological disorders, including those diagnosed with AD (n=23) and those not (n=4). Left eyes were fixed in 10% formalin. Retinas were stained with 0.1% Thioflavin-S and counterstained with DAPI, flat mounted in quadrants, and imaged using a microscope fitted with a polarimeter. Presumed Aβ deposits (PAβ) were counted using fluorescence (FL) and polarimetry (Pol) signals and quadrants not examined were given a value equal to other quadrants’ averages. Brains were examined and AD pathology determined (NIA guidelines) based on assessment of anatomical distribution of Aβ deposits (Thal phase, TP), anatomical distribution of tau-immunoreactive neurofibrillary tangles (Braak stage, BS), assessment of neuritic senile plaque numbers (NP), and a cumulative score of the severity of AD pathology (CSS). Diffuse plaque numbers (DP) were also assessed. Counts of retinal amyloid deposits found in anterior retina with FL and/or Pol signals were compared to these measures.
Most PAβ deposits with FL signals also had Pol signals with 93.2% sensitivity and 92.8% specificity. No PAβ deposits were found in the retinas of the individuals with no AD pathology (n=2, CSS=0). PAβ occurred in every retina from those with AD brain pathology. The Spearman’s rhos (ρ) between the number of retinal PAβ deposits and CSS, TP, BS and DP were significant but insignificant for NP. Gamma scores showed moderate relationships for TP, BS and DP (γ=0.53,0.59,0.53) and a weak relationship for CSS (γ=0.47) and NP (γ=0.38). However, the average number of retinal deposits for none to low CSS are less than that for intermediate to high CSS (p < 0.03).
Retinal amyloid deposits are an early marker for the presence of AD brain pathology. Their number has significant correlations to all brain pathology scores except for NP. Thus, in vivo retinal imaging of Aβ is a promising diagnostic tool of AD brain pathology.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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