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APP21 transgenic rats develop age‐dependent cognitive impairment and microglia accumulation within white matter tracts
Author(s) -
Liu Qingfan,
Weishaupt Nina,
Shin Sheojung,
Singh Ramandeep,
Agca Yuksel,
Agca Cansu,
Hachinski Vladimir,
Whitehead Shawn
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.802.53
Subject(s) - microglia , white matter , genetically modified mouse , morris water navigation task , transgene , neuroscience , disease , medicine , cognition , wild type , psychology , pathology , inflammation , biology , magnetic resonance imaging , biochemistry , gene , mutant , radiology
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. Support or Funding Information We appreciate funding support from the Ontario Mental Health Foundation, and funding from the Canadian Institutes for Health Research, Canadian Consortium on Neurodegeneration in Aging and Canadian Foundation of Innovation. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .