Affiliations: [a] Neurodegeneration Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA | [b] Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA
Correspondence:
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Correspondence to: Nasser H. Zawia, PhD, University of Rhode Island, Pharmacy Building, 7 Greenhouse Road, Kingston, RI 02881, USA. Tel.: +1 401 874 2663; Fax: +1 401 874 2181; E-mail: [email protected].
Abstract: We have previously reported that tolfenamic acid treatment decreases the amyloidogenic proteins in C57BL/6 and in old hemizygous R1.40 transgenic mice via the degradation of the transcription factor specificity 1 protein (Sp1). The lowering of amyloid-β protein precursor (AβPP) and amyloid-β (Aβ) in hemizygous R1.40 transgenic mice was accompanied by reversal of the identified spatial reference and working memory deficits observed in the mouse model. In this study, we examined the ability of tolfenamic acid to reduce the amyloid plaque burden, as well as to ameliorate spatial learning and memory deficits in homozygous R1.40 mice. Results from immunohistochemical analysis indicated that tolfenamic acid treatment resulted in a profound decrease in cerebral Aβ plaque burden that was accompanied by improvements in spatial working memory assessed by spontaneous alternation ratio in the Y-maze. These results provide further evidence that tolfenamic acid could be utilized as a repurposed drug to modify Alzheimer's disease pathogenesis.
Keywords: AD transgenic mouse model, Alzheimer's disease, amyloid-β plaque burden, immunohistochemistry, learning and memory, Morris water maze, tolfenamic acid, Y-maze
