No improvement after chronic ibuprofen treatment in the 5XFAD mouse model of Alzheimer%26apos;s disease

作者：Hillmann Antje; Hahn Stefanie; Schilling Stephan; Hoffmann Torsten; Demuth Hans Ulrich; Bulic Bruno; Schneider Axmann Thomas; Bayer Thomas A; Weggen Sascha; Wirths Oliver^*

来源：Neurobiology of Aging, 2012, 33(4): 833.e39.

DOI：10.1016/j.neurobiolaging.2011.08.006

• Amyloid
• Ibuprofen
• Transgenic mice
• Inflammation
• gamma-Secretase modulation
• Behavior
• Presenilin
• Alzheimer%26apos
• s disease

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that has been reported to reduce the risk of developing Alzheimer%26apos;s disease (AD). Its preventive effects in AD are likely pleiotropic as ibuprofen displays both anti-inflammatory activity by inhibition of cyclooxygenases and anti-amyloidogenic activity by modulation of gamma-secretase. In order to study the anti-inflammatory properties of ibuprofen independent of its anti-amyloidogenic activity, we performed a long-term treatment study with ibuprofen in 5XFAD mice expressing a presenilin-1 mutation that renders this AD model resistant to gamma-secretase modulation. As expected, ibuprofen treatment for 3 months resulted in a reduction of the inflammatory reaction in the 5XFAD mouse model. Importantly, an unchanged amyloid beta (A beta) plaque load, an increase in soluble A beta 42 levels, and an aggravation of some behavioral parameters were noted, raising the question whether suppression of inflammation by nonsteroidal anti-inflammatory drug is beneficial in AD.

• 出版日期2012-4