Association of Cognitive Function with Amyloid-β and Tau Proteins in the Vitreous Humor
- PMID: 30856114
- PMCID: PMC6850770
- DOI: 10.3233/JAD-181104
Association of Cognitive Function with Amyloid-β and Tau Proteins in the Vitreous Humor
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; Mini-Mental State Exam; amyloid-β; dementia; ocular biomarkers; tau; vitreous.
Figures
Similar articles
-
Neurofilament light chain in the vitreous humor of the eye.Alzheimers Res Ther. 2020 Sep 17;12(1):111. doi: 10.1186/s13195-020-00677-4. Alzheimers Res Ther. 2020. PMID: 32943089 Free PMC article.
-
Cognitive function in very old men does not correlate to biomarkers of Alzheimer's disease.BMC Geriatr. 2017 Sep 8;17(1):208. doi: 10.1186/s12877-017-0601-6. BMC Geriatr. 2017. PMID: 28886705 Free PMC article.
-
Reciprocal Predictive Relationships between Amyloid and Tau Biomarkers in Alzheimer's Disease Progression: An Empirical Model.J Neurosci. 2019 Sep 11;39(37):7428-7437. doi: 10.1523/JNEUROSCI.1056-19.2019. Epub 2019 Jul 26. J Neurosci. 2019. PMID: 31350262 Free PMC article.
-
Cognitive Decline in Preclinical Alzheimer's Disease: Amyloid-Beta versus Tauopathy.J Alzheimers Dis. 2018;61(1):265-281. doi: 10.3233/JAD-170490. J Alzheimers Dis. 2018. PMID: 29154274 Free PMC article. Review.
-
Amyloid beta protein and tau in cerebrospinal fluid and plasma as biomarkers for dementia: a review of recent literature.Curr Clin Pharmacol. 2008 May;3(2):123-31. doi: 10.2174/157488408784293723. Curr Clin Pharmacol. 2008. PMID: 18700307 Review.
Cited by 8 articles
-
Alzheimer's Disease Seen through the Eye: Ocular Alterations and Neurodegeneration.Int J Mol Sci. 2022 Feb 24;23(5):2486. doi: 10.3390/ijms23052486. Int J Mol Sci. 2022. PMID: 35269629 Free PMC article. Review.
-
Association of tear fluid amyloid and tau levels with disease severity and neurodegeneration.Sci Rep. 2021 Nov 22;11(1):22675. doi: 10.1038/s41598-021-01993-x. Sci Rep. 2021. PMID: 34811435 Free PMC article.
-
Protein and Imaging Biomarkers in the Eye for Early Detection of Alzheimer's Disease.J Alzheimers Dis Rep. 2021 May 3;5(1):375-387. doi: 10.3233/ADR-210283. J Alzheimers Dis Rep. 2021. PMID: 34189409 Free PMC article. Review.
-
Systemic delivery of a specific antibody targeting the pathological N-terminal truncated tau peptide reduces retinal degeneration in a mouse model of Alzheimer's Disease.Acta Neuropathol Commun. 2021 Mar 9;9(1):38. doi: 10.1186/s40478-021-01138-1. Acta Neuropathol Commun. 2021. PMID: 33750467 Free PMC article.
-
Role of Retinal Amyloid-β in Neurodegenerative Diseases: Overlapping Mechanisms and Emerging Clinical Applications.Int J Mol Sci. 2021 Feb 26;22(5):2360. doi: 10.3390/ijms22052360. Int J Mol Sci. 2021. PMID: 33653000 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grant support
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous