Abstract
Alzheimer's disease (AD) is an ageing-related neurodegenerative disease characterized and diagnosed by deposition of insoluble amyloid-β (Aβ) plaques in the brain. The plaque accumulation in the brain directly affects reduced levels of Aβ in cerebrospinal fluid (CSF) and blood, as Aβ can freely transport the blood-brain barrier, and clinical investigations have suggested these two biofluids as promising samples for in vitro diagnosis. Given that the human eye structurally resembles the brain and Aβ accumulation often observed in the ocular region of AD patients, in this study, we examined aqueous humor Aβ as another possible surrogate biomarker. First, using the acute Aβ-infused AD mouse model by injecting Aβ to the CSF in intracerebroventricular region of normal ICR mice, we investigated whether Aβ concentration in the aqueous humor in AD models is positively correlated with the concentration in the CSF. Then, we examined the correlation of aqueous humor Aβ levels with increased plaque deposition in the brain and reduced Aβ levels in both CSF and blood in adult and aged 5XFAD Alzheimer transgenic mice. Collectively, the synthetic Aβ injected into CSF immediately migrate to the aqueous humor, however, the age-dependently reducing pattern of Aβ levels in CSF and blood was not observed in the aqueous humor.
Highlights
Increased production and deposition of the amyloid-β (Aβ) peptide in human nervous system is a typical characteristic of Alzheimer disease (AD) [1]
During the pathological progression of AD, the amyloid precursor protein (APP) on the membrane of neurons is sequentially cleaved by β- and γ-secretases and releases excessive Aβ to the extracellular regions
In AD animal mice, we observed that (1) Aβ(1–42) monomers infused into cerebrospinal fluid (CSF) in the ICV region acutely transport to the blood and the aqueous humor, (2) artificially injected Aβ(1–42) levels in CSF are proportionally reflected in the aqueous humor in mice without human APP expression, and (3) the progressive decrease of Aβ(1–42) levels in representative fluid biomarkers, CSF and blood, is not observed in aqueous humor
Summary
Increased production and deposition of the amyloid-β (Aβ) peptide in human nervous system is a typical characteristic of Alzheimer disease (AD) [1]. During the pathological progression of AD, the amyloid precursor protein (APP) on the membrane of neurons is sequentially cleaved by β- and γ-secretases and releases excessive Aβ to the extracellular regions. Alterations of aqueous humor Aβ levels in AD mouse models
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