Bruch’s Membrane Changes in a Transgenic Mice Model of Alzheimer’s Disease

Abstract

 

Purpose:

 

Age-related macular degeneration (AMD) and Alzheimer’s disease (AD) share almost identical genetic and environmental risk factors and similar molecular processes. The purpose of this study was to examine whether deposit formation in the brain is associated with changes in protein and zinc deposition in Bruch’s membrane (BM) in a transgenic animal model for AD.

 

Methods:

 

APP/PS1 transgenic mice model of AD was used to study ultra structural changes of BM. BM thickness were measured at segments where the choriocapillary lumen was both open and lined by a single layer of endothelium, avoiding the intercapillary pillars, far periphery and optic nerve. Ten measurements were made in segments of equal length form 10 pictures from each mouse using Image J 1.43. Zinc in BM was detected using autometallography.

 

Results:

 

Our data confirms earlier reports showing a thickening of BM with normal ageing. At 4 month the average thickness of BM in wild type animals was 0.345 ± 0.047 µm that increased to 0.63 ± 0.12 µm by 12 months. However, in the transgenic groups BM was already thickened at 4 month (0.53 ± 0.04 µm). At 12 months there was a dramatic increase in BM thickenss (1.21 ± 0.07 µm) accompanied by the appearance of sub-RPE deposits. There was substantially more zinc in BM in transgenic animals compared to wild type. Injection of DEDTC (a zinc selective chelator) completely abolished autometallographic labelling of zinc.

 

Conclusions:

 

The APP/PS1 transgenic mice have a thickened Bruch’s membrane and sub-RPE deposits are clearly visible. This thickening is associated with increased zinc deposition. These might be relevant to understand how sub-RPE deposits are formed but also important in strengthening further the potential association between AMD and AD. Importantly, this transgenic model for AD may represent a model to study early deposit formation leading to retinal degeneration and blindness in AMD.

 

Keywords: age-related macular degeneration • Bruch's membrane • extracellular matrix