Dataset Information

Alterations of aqueous humor A? levels in A?-infused and transgenic mouse models of Alzheimer disease.

ABSTRACT: Alzheimer's disease (AD) is an ageing-related neurodegenerative disease characterized and diagnosed by deposition of insoluble amyloid-? (A?) plaques in the brain. The plaque accumulation in the brain directly affects reduced levels of A? in cerebrospinal fluid (CSF) and blood, as A? 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 A? accumulation often observed in the ocular region of AD patients, in this study, we examined aqueous humor A? as another possible surrogate biomarker. First, using the acute A?-infused AD mouse model by injecting A? to the CSF in intracerebroventricular region of normal ICR mice, we investigated whether A? 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 A? levels with increased plaque deposition in the brain and reduced A? levels in both CSF and blood in adult and aged 5XFAD Alzheimer transgenic mice. Collectively, the synthetic A? injected into CSF immediately migrate to the aqueous humor, however, the age-dependently reducing pattern of A? levels in CSF and blood was not observed in the aqueous humor.

SUBMITTER: Kwak DE

PROVIDER: S-EPMC6953883 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Alterations of aqueous humor Aβ levels in Aβ-infused and transgenic mouse models of Alzheimer disease.

Kwak Da Eun DE Ko Taeho T Koh Han Seok HS Ji Yong Woo YW Shin Jisu J Kim Kyeonghwan K Kim Hye Yun HY Lee Hyung-Keun HK Kim YoungSoo Y

PloS one 20200110 1

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 ...[more]

PMID: 31923257

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Project description:Fuchs endothelial corneal dystrophy (FECD) is a progressive disorder characterized by corneal endothelial decompensation leading to corneal edema, clouding, and vision impairment. Despite improved understanding over the last century since its first description, the exact mechanism(s) behind the pathogenesis of FECD remain unknown, and surgical correction is the only effective treatment available. Previous studies have suggested a role for changes in aqueous humor (AH) composition in FECD pathogenesis, so to explore this possibility, we probed the AH proteome for alterations correlating with end-stage corneal disease. Following albumin depletion we performed label-free quantitative tandem mass spectrometry on proteins isolated from patients with and without FECD who were scheduled to undergo routine cataract extraction. We identified 64 proteins, most of which were identified in previous AH proteomic studies of patients with cataracts, in the albumin-depleted fraction. The levels of five of these were significantly lower (afamin, complement C3, histidine-rich glycoprotein, immunoglobulin heavy [IgH], and protein family with sequence similarity 3, member C [FAM3C]), while the levels of one (suprabasin) was significantly higher in patients with FECD compared to controls (p?0.01). We also identified 34 proteins in the albumin-bound fraction, four of which were significantly elevated in patients with FECD including a hemoglobin fragment, immunoglobulin kappa (IgK), immunoglobulin lambda (IgL), and uncharacterized protein albumin (ALB), (p?0.01). Although it has been reported that females have a greater extent of disease than males, we were unable to detect any significant differences in protein levels due to gender. Because FECD is a progressive disorder, regression analyses were performed to determine any significant correlations with age, and of interest retinol-binding protein 3 was significantly correlated with age in patients with FECD (p?0.01), whereas no proteins in the control group correlated with age. This is the first report indicating alterations in the AH proteome with FECD, and taken together this study suggests several novel hypotheses regarding AH proteins role in FECD pathogenesis.

Dataset Information

Alterations of aqueous humor A? levels in A?-infused and transgenic mouse models of Alzheimer disease.

Publications

Alterations of aqueous humor Aβ levels in Aβ-infused and transgenic mouse models of Alzheimer disease.

Similar Datasets

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