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Istradefylline reduces memory deficits in aging mice with amyloid pathology.

TitleIstradefylline reduces memory deficits in aging mice with amyloid pathology.
Publication TypeJournal Article
Year of Publication2018
AuthorsOrr AG, Lo I, Schumacher H, Ho K, Gill M, Guo W, Kim DH, Knox A, Saito T, Saido TC, Simms J, Toddes C, Wang X, Yu G-Q, Mucke L
JournalNeurobiol Dis
Volume110
Pagination29-36
Date Published2018 Feb
ISSN1095-953X
Abstract

Adenosine A receptors are putative therapeutic targets for neurological disorders. The adenosine A receptor antagonist istradefylline is approved in Japan for Parkinson's disease and is being tested in clinical trials for this condition elsewhere. A 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 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 receptor blockers might help counteract memory problems in patients with Alzheimer's disease.

DOI10.1016/j.nbd.2017.10.014
Alternate JournalNeurobiol. Dis.
PubMed ID29100987
PubMed Central IDPMC5747997
Grant ListP50 AG023501 / AG / NIA NIH HHS / United States
R00 AG048222 / AG / NIA NIH HHS / United States
P30 NS065780 / NS / NINDS NIH HHS / United States
K99 AG048222 / AG / NIA NIH HHS / United States
C06 RR018928 / RR / NCRR NIH HHS / United States