Journal
NEUROBIOLOGY OF AGING
Volume 58, Issue -, Pages 112-119Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2017.06.020
Keywords
Alzheimer's disease; Amyloid-beta; Sheep Ovis aries; Plaques; Tangles; Animal model
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Funding
- Freemasons of New Zealand
- Knut and Alice Walleberg Foundation
- Swedish Research Council
- European Research Council
- Swedish Alzheimer Foundation
- Swedish Brain Foundation
- Torsten Soderberg Foundation
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This study reports the identification and characterization of markers of Alzheimer's disease (AD) in aged sheep (Ovis aries) as a preliminary step toward making a genetically modified large animal model of AD. Importantly, the sequences of key proteins involved in AD pathogenesis are highly conserved between sheep and human. The processing of the amyloid-beta (Ab) protein is conserved between sheep and human, and sheep A beta(1-42)/A beta(1-40) ratios in cerebrospinal fluid (CSF) are also very similar to human. In addition, total tau and neurofilament light levels in CSF are comparable with those found in human. The presence of neurofibrillary tangles in aged sheep brain has previously been established; here, we report for the first time that plaques, the other pathologic hallmark of AD, are also present in the aged sheep brain. In summary, the biological machinery to generate the key neuropathologic features of AD is conserved between the human and sheep, making the sheep a good candidate for future genetic manipulation to accelerate the condition for use in pathophysiological discovery and therapeutic testing. (C) 2017 Elsevier Inc. All rights reserved.
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