Dataset Information

A longitudinal assessment of retinal function and structure in the APP/PS1 transgenic mouse model of Alzheimer's disease.

ABSTRACT:

Background

A great body of evidence suggests that there are retinal functional and structural changes that occur in Alzheimer's disease (AD). However, whether such changes are primary or secondary remains to be elucidated. We studied a range of retinal functional and structural parameters in association with AD- specific pathophysiological markers in the double transgenic APP/PS1 and control mice across age.

Methods

Electroretinogram (ERG) and optical coherence tomography (OCT) was performed in APP/PS1 and wild type (WT) control mice every 3 months from 3 to 12?months of age. For functional assessment, the a- and b-wave of the ERG, amplitude of oscillatory potentials (OP) and the positive scotopic threshold response (pSTR) were quantified at each time point. For structural assessment, the inner and outer retinal thickness was segmented and measured from OCT scans. Episodic memory was evaluated at 6, 9 and 12?months of age using the novel object recognition test. Amyloid beta (A?) distribution in the hippocampus and the retina were visualised at 3, 6 and 12?months of age. Inter- and intra- group analysis was performed to study rate of change for each parameter between the two groups.

Results

Inter-group analysis revealed a significant difference in b-wave and OPs of APP/PS1 compared to WT controls starting from 3?months (p?p?p?ConclusionsWe observed an age-related decline in retinal functional and structural parameters in both APP/PS1 and WT controls, however, inter-group analysis revealed that inner retinal functional and structural decline is exacerbated in APP/PS1 mice, and that retinal functional changes precede structural changes in this strain. Further studies are required to confirm whether such phenomenon occurs in humans and if studying retinal functional changes can aid-in early assessment of AD.

SUBMITTER: Georgevsky D

PROVIDER: S-EPMC6774218 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

A longitudinal assessment of retinal function and structure in the APP/PS1 transgenic mouse model of Alzheimer's disease.

Georgevsky Dana D Retsas Stephanie S Raoufi Newsha N Shimoni Olga O Golzan S Mojtaba SM

Translational neurodegeneration 20191001

<h4>Background</h4>A great body of evidence suggests that there are retinal functional and structural changes that occur in Alzheimer's disease (AD). However, whether such changes are primary or secondary remains to be elucidated. We studied a range of retinal functional and structural parameters in association with AD- specific pathophysiological markers in the double transgenic APP/PS1 and control mice across age.<h4>Methods</h4>Electroretinogram (ERG) and optical coherence tomography (OCT) wa ...[more]

PMID: 31592131

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Project description:IntroductionThe disintegrin and metalloproteinase 17 (ADAM17) exhibits α-secretase activity, whereby it can prevent the production of neurotoxic amyloid precursor protein-α (APP). ADAM17 is abundantly expressed in vascular endothelial cells and may act to regulate vascular homeostatic responses, including vasomotor function, vascular wall morphology, and formation of new blood vessels. The role of vascular ADAM17 in neurodegenerative diseases remains poorly understood. Here, we hypothesized that cerebrovascular ADAM17 plays a role in the pathogenesis of Alzheimer's disease (AD).Methods and resultsWe found that 9-10 months old APP/PS1 mice with b-amyloid accumulation and short-term memory and cognitive deficits display a markedly reduced expression of ADAM17 in cerebral microvessels. Systemic delivery and adeno-associated virus (AAV)-mediated re-expression of ADAM17 in APP/PS1 mice improved cognitive functioning, without affecting b-amyloid plaque density. In isolated and pressurized cerebral arteries of APP/PS1 mice the endothelium-dependent dilation to acetylcholine was significantly reduced, whereas the vascular smooth muscle-dependent dilation to the nitric oxide donor, sodium nitroprusside was maintained when compared to WT mice. The impaired endothelium-dependent vasodilation of cerebral arteries in APP/PS1 mice was restored to normal level by ADAM17 re-expression. The cerebral artery biomechanical properties (wall stress and elasticity) and microvascular network density was not affected by ADAM17 re-expression in the APP/PS1 mice. Additionally, proteomic analysis identified several differentially expressed molecules involved in AD neurodegeneration and neuronal repair mechanisms that were reversed by ADAM17 re-expression.DiscussionThus, we propose that a reduced ADAM17 expression in cerebral microvessels impairs vasodilator function, which may contribute to the development of cognitive dysfunction in APP/PS1 mice, and that ADAM17 can potentially be targeted for therapeutic intervention in AD.

Dataset Information

A longitudinal assessment of retinal function and structure in the APP/PS1 transgenic mouse model of Alzheimer's disease.

Background

Methods

Results

Publications

A longitudinal assessment of retinal function and structure in the APP/PS1 transgenic mouse model of Alzheimer's disease.

Similar Datasets

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