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

Journal of Neuroinflammation
Nina WeishauptShawn Narain Whitehead

Abstract

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. 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. 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 ...Continue Reading

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Citations

Jul 23, 2019·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Vladimir HachinskiZaven S Khachaturian
Sep 30, 2020·EJNMMI Research·Nassir U Al-KhishmanJonathan D Thiessen
Jul 11, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Nadja Van CampHervé Boutin

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Methods Mentioned

BETA
transgenic
PCR

Software Mentioned

Nikon Elements
ANY
maze
Activity Monitor
ImageJ

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