Association of Cognitive Function with Amyloid-β and Tau Proteins in the Vitreous Humor

Article type: Research Article

Authors: Wright, Lauren M.^a | Stein, Thor D.^{b; c; d; e} | Jun, Gyungah^{f; g} | Chung, Jaeyoon^{f; g} | McConnell, Kate^a | Fiorello, Marissa^a | Siegel, Nicole^a | Ness, Steven^a | Xia, Weiming^{e; h} | Turner, Kelley L.^a | Subramanian, Manju L.^{a; *}

Affiliations: [a] Department of Ophthalmology, Boston University School of Medicine, Boston Medical Center, Boston, MA, USA | [b] Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston Medical Center, Boston, MA, USA | [c] Department of Veterans Affairs Medical Center, Bedford, MA, USA | [d] VA Boston Healthcare System, Boston, MA, USA | [e] Boston University Alzheimer’s Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA | [f] Department of Genetics, Boston University School of Medicine, Boston Medical Center, Boston, MA, USA | [g] Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA | [h] Department of Pharmacology and Experimental Therapeutics, Veterans Affairs Medical Center, Bedford, MA, USA

Correspondence: [*] Correspondence to: Manju Subramanian, MD, 85 E Concord St 8th floor, Boston MA 02118, USA. Tel.: +1 617 638 4555; E-mail: Manju.Subramanian@bmc.org.

Abstract: Background:The eye may serve as source for diagnostic testing for early detection of Alzheimer’s disease (AD). Examination of amyloid-β (Aβ) and tau protein content in human vitreous and its correlation to neuro-cognition may improve ocular-based AD detection methods. Objective:To evaluate levels of Aβ and tau protein in human vitreous humor and investigate the clinical predictive role of these proteins as early diagnostic markers of AD. Methods:A prospective, single-center, multi-surgeon cohort study. Vitreous humor samples from 80 eyes were measured quantitatively for Aβ40-42, pTau, and tTau. Linear regression was used to test associations between AD biomarker levels, Mini-Mental State Exam (MMSE), and serum apolipoprotein E (APOE) allele status, with adjustment for age, sex, and education level of patients. Results:Lower MMSE scores were significantly associated with lower levels of vitreous Aβ40 (p = 0.015), Aβ42 (p = 0.0066), and tTau (p = 0.0085), and these biomarkers were not associated with any pre-existing eye conditions. Presence of the ɛ4 allele and the ɛ2 allele approached significance with reduced Aβ40 level (p = 0.053) and increased p-Tau level (p = 0.056), respectively. Conclusion:Patients with poor cognitive function have significantly lower vitreous humor levels of AD-related biomarkers Aβ40, Aβ42, and tTau. These biomarkers do not correlate with underlying eye conditions, suggesting their specificity in association with cognitive change. This is the first study to our knowledge to correlate cognition with AD-related proteins in the vitreous humor. Results suggest ocular proteins may have a role for early dementia detection in individuals at risk for AD.

Keywords: Alzheimer’s disease, amyloid-β, dementia, Mini-Mental State Exam, ocular biomarkers, tau, vitreous

DOI: 10.3233/JAD-181104

Journal: Journal of Alzheimer's Disease, vol. 68, no. 4, pp. 1429-1438, 2019