Ibuprofen reduces Abeta, hyperphosphorylated tau and memory deficits in Alzheimer mice.
We examined the effects of ibuprofen on cognitive deficits, Abeta and tau accumulation in young triple transgenic (3xTg-AD) mice. 3xTg-AD mice were fed ibuprofen-supplemented chow between 1 and 6 months. Untreated 3xTg-AD mice showed significant impairment in the ability to learn the Morris water maze (MWM) task compared to age-matched wild-type (WT) mice. The performance of 3xTg-AD mice was significantly improved with ibuprofen treatment compared to untreated 3xTg-AD mice. Ibuprofen-treated transgenic mice showed a significant decrease in intraneuronal oligomeric Abeta and hyperphosphorylated tau (AT8) immunoreactivity in the hippocampus. Confocal microscopy demonstrated co-localization of conformationally altered (MC1) and early phosphorylated tau (CP-13) with oligomeric Abeta, and less co-localization of oligomeric Abeta and later forms of phosphorylated tau (AT8 and PHF-1) in untreated 3xTg-AD mice. Our findings show that prophylactic treatment of young 3xTg-AD mice with ibuprofen reduces intraneuronal oligomeric Abeta, reduces cognitive deficits, and prevents hyperphosphorylated tau immunoreactivity. These findings provide further support for intraneuronal Abeta as a cause of cognitive impairment, and suggest that pathological alterations of tau are associated with intraneuronal oligomeric Abeta accumulation.
McKee
Ann C
AC
Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Carreras
Isabel
I
Hossain
Lokman
L
Ryu
Hoon
H
Klein
William L
WL
Oddo
Salvatore
S
LaFerla
Frank M
FM
Jenkins
Bruce G
BG
Kowall
Neil W
NW
Dedeoglu
Alpaslan
A
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000544:Alzheimer Disease / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use*; D007211:Indoles; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D053764:Presenilin-1 / Q000235:genetics; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016861:Cyclooxygenase Inhibitors; D004268:DNA-Binding Proteins; D007211:Indoles; D053764:Presenilin-1; D016875:tau Proteins; C007293:DAPI; D000251:Adenosine Triphosphatases; D007052:Ibuprofen