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Clayton Wisely, Cason Robbins, Justin Ma, Terry Kim, Dilraj Grewal, Sharon Fekrat; Correlation of aqueous humor and plasma concentrations of amyloid and tau in older adults without dementia. Invest. Ophthalmol. Vis. Sci. 2021;62(8):543.
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© ARVO (1962-2015); The Authors (2016-present)
Plasma and cerebrospinal fluid (CSF) levels of protein biomarkers have been associated with Alzheimer’s disease (AD). Limited prior studies have suggested amyloid beta 40 (Aβ40) and 42 (Aβ42) are present in human aqueous, but detection of tau proteins has not been previously reported. We sought to characterize normal concentrations of Aβ40, Aβ42, and total tau in human aqueous and compare to plasma concentrations and Montreal Cognitive Assessment (MoCA) scores.
Twenty adults with no history of dementia underwent simultaneous aqueous and plasma sampling and MoCA (blind version) testing at the time of cataract surgery. Aqueous and plasma samples underwent analysis in duplicate using the single-molecule array (SiMoA) SR-X platform (Quanterix®, Middlesex, MA) to measure Aβ40, Aβ42, and total tau.
Mean (standard deviation) age was 70.7 (6.6) years. Mean MoCA score was 19.3 (2.5). Two subjects were unable to give plasma. Three of 18 (17%) plasma samples could not be analyzed via SiMoA. Mean measured aqueous concentrations (pg/ml) of Aβ40, Aβ42, and total tau were 131.0 (67.1), 3.6 (3.6), and 39.2 (41.2) respectively, and corresponding plasma concentrations were 128.5 (57.2), 10.2 (5.7), and 5.6 (3.2). All aqueous samples contained Aβ40 and total tau, but only 3/20 (15%) of samples contained detectable Aβ42. All analyzed plasma samples (n=15) had detectable Aβ40, Aβ42, and total tau. Comparisons between first and second runs of aqueous samples demonstrated mean difference of 18% (24%) for Aβ40 and 14% (15%) for total tau. There were minimal correlations between Aβ40 (r2 < 0.01) and total tau (r2 = 0.11) in aqueous and plasma. Aqueous concentrations of Aβ40 and total tau also demonstrated minimal correlation with MoCA scores, r2 = 0.07 and 0.02 respectively or age, r2 = 0.01 and 0.20 respectively.
SiMoA can measure Aβ40 and total tau in human aqueous. Aβ42 was not detectable in 85% of aqueous samples but was detectable in all plasma samples. In adults without dementia, there is minimal correlation between aqueous and plasma concentrations of Aβ40 and total tau. Aqueous concentrations of Aβ40 and total tau do not appear to correlate with MoCA scores. Further study in subjects with AD is indicated to determine whether aqueous Aβ40 and total tau may differ between AD and controls or correlate with cognitive test scores or CSF protein concentrations.
This is a 2021 ARVO Annual Meeting abstract.
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