Triflusal reduces dense-core plaque load, associated axonal alterations and inflammatory changes, and rescues cognition in a transgenic mouse model of Alzheimer's disease.
Inflammation has been associated with the two classic lesions in the Alzheimer's (AD) brain, amyloid deposits and neurofibrillary tangles. Recent data suggest that Triflusal, a compound with potent anti-inflammatory effects in the central nervous system in vivo, might delay the conversion from amnestic mild cognitive impairment to a fully established clinical picture of dementia. In the present study, we investigated the effect of Triflusal on brain Abeta accumulation, neuroinflammation, axonal curvature and cognition in an AD transgenic mouse model (Tg2576). Triflusal treatment did not alter the total brain Abeta accumulation but significantly reduced dense-cored plaque load and associated glial cell proliferation, proinflammatory cytokine levels and abnormal axonal curvature, and rescued cognitive deficits in Tg2576 mice. Behavioral benefit was found to involve increased expression of c-fos and BDNF, two of the genes regulated by CREB, as part of the signal transduction cascade underlying the molecular basis of long-term potentiation. These results add preclinical evidence of a potentially beneficial effect of Triflusal in AD.
Neurology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
M
M
Coma
L
L
Serenó
B
B
Da Rocha-Souto
T C
TC
Scotton
J
J
España
M B
MB
Sánchez
M
M
Rodríguez
J
J
Agulló
C
C
Guardia-Laguarta
M
M
Garcia-Alloza
L A
LA
Borrelli
J
J
Clarimón
A
A
Lleó
B J
BJ
Bacskai
C A
CA
Saura
B T
BT
Hyman
T
T
Gómez-Isla
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002491:Central Nervous System Agents / Q000494:pharmacology*; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012459:Salicylates / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D002491:Central Nervous System Agents; D016207:Cytokines; D016760:Proto-Oncogene Proteins c-fos; D012459:Salicylates; C016167:triflusal