1. Istradefylline reduces memory deficits in aging mice with amyloid pathology.
- Author
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Orr, Anna G., Lo, Iris, Schumacher, Heike, Ho, Kaitlyn, Gill, Michael, Guo, Weikun, Kim, Daniel H., Knox, Anthony, Saito, Takashi, Saido, Takaomi C., Simms, Jeffrey, Toddes, Carlee, Wang, Xin, Yu, Gui-Qiu, and Mucke, Lennart
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ADENOSINES , *CELL receptors , *NEUROLOGICAL disorders , *ALZHEIMER'S disease , *ASTROCYTES - Abstract
Adenosine A 2A receptors are putative therapeutic targets for neurological disorders. The adenosine A 2A receptor antagonist istradefylline is approved in Japan for Parkinson's disease and is being tested in clinical trials for this condition elsewhere. A 2A receptors on neurons and astrocytes may contribute to Alzheimer's disease (AD) by impairing memory. However, it is not known whether istradefylline enhances cognitive function in aging animals with AD-like amyloid plaque pathology. Here, we show that elevated levels of Aβ, C-terminal fragments of the amyloid precursor protein (APP), or amyloid plaques, but not overexpression of APP per se, increase astrocytic A 2A receptor levels in the hippocampus and neocortex of aging mice. Moreover, in amyloid plaque-bearing mice, low-dose istradefylline treatment enhanced spatial memory and habituation, supporting the conclusion that, within a well-defined dose range, A 2A receptor blockers might help counteract memory problems in patients with Alzheimer's disease. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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