Title

APP21 transgenic rats develop age-dependent cognitive impairment and microglia accumulation within white matter tracts.

Authors

Nina Weishaupt, Western University
Qingfan Liu, Western University
Sheojung Shin, Western University
Ramandeep Singh, Western University
Yuksel Agca
Cansu Agca
Vladimir Hachinski, Western University
Shawn Narain Whitehead, Western UniversityFollow

Document Type

Article

Publication Date

8-28-2018

Journal

Journal of Neuroinflammation [electronic resource]

Volume

15

Issue

1

First Page

241

Last Page

241

URL with Digital Object Identifier

https://doi.org/10.1186/s12974-018-1273-7

Abstract

Background

Most of the animal models commonly used for preclinical research into Alzheimer's disease (AD) largely fail to address the pathophysiology, including the impact of known risk factors, of the widely diagnosed sporadic form of the disease. Here, we use a transgenic rat (APP21) that does not develop AD-like pathology spontaneously with age, but does develop pathology following vascular stress. To further the potential of this novel rat model as a much-needed pre-clinical animal model of sporadic AD, we characterize APP21 transgenic rats behaviorally and histologically up to 19 months of age.

Methods

The open field test was used as a measure of activity; and the Morris water maze was used to assess learning, memory, and strategy shift. Neuronal loss and microglia activation were also assessed throughout the brain.

Results

APP21 transgenic rats showed deficits in working memory from an early age, yet memory recall performance after 24 and 72 h was equal to that of wildtype rats and did not deteriorate with age. A deficit in strategy shift was observed at 19 months of age in APP21 transgenic rats compared to Fischer wildtype rats. Histologically, APP21 transgenic rats demonstrated accelerated white matter inflammation compared to wildtype rats, but interestingly no differences in neuron loss were observed.

Conclusions

The combined presence of white matter pathology and executive function deficits mirrored what is often found in patients with mild cognitive impairment or early dementia, and suggests that this rat model will be useful for translationally meaningful studies into the development and prevention of sporadic AD. The presence of widespread white matter inflammation as the only observed pathological correlate for cognitive deficits raises new questions as to the role of neuroinflammation in cognitive decline.

Notes

Article originally published at Journal of Neuroinflammation

https://doi.org/10.1186/s12974-018-1273-7

© 2018 The Author(s)