Beneficial effects of caffeine in a transgenic model of Alzheimer's disease-like tau pathology.
Tau pathology found in Alzheimer's disease (AD) is crucial in cognitive decline. Epidemiologic evidences support that habitual caffeine intake prevents memory decline during aging and reduces the risk to develop Alzheimer's disease. So far, experimental studies addressed the impact of caffeine in models mimicking the amyloid pathology of AD. However, in vivo effects of caffeine in a model of AD-like tauopathy remain unknown. Here, we evaluated effects of chronic caffeine intake (0.3 g/L through drinking water), given at an early pathologic stage, in the THY-Tau22 transgenic mouse model of progressive AD-like tau pathology. We found that chronic caffeine intake prevents from the development of spatial memory deficits in tau mice. Improved memory was associated with reduced hippocampal tau phosphorylation and proteolytic fragments. Moreover, caffeine treatment mitigated several proinflammatory and oxidative stress markers found upregulated in the hippocampus of THY-Tau22 animals. Together, our data support that moderate caffeine intake is beneficial in a model of AD-like tau pathology, paving the way for future clinical evaluation in AD patients.
Université Lille-Nord de France, UDSL, Lille, France; Inserm U837, Jean-Pierre Aubert Research Centre, IMPRT, Lille France.
Cyril
C
Laurent
Université Lille-Nord de France, UDSL, Lille, France; Inserm U837, Jean-Pierre Aubert Research Centre, IMPRT, Lille France.
Sabiha
S
Eddarkaoui
Université Lille-Nord de France, UDSL, Lille, France; Inserm U837, Jean-Pierre Aubert Research Centre, IMPRT, Lille France.
Maxime
M
Derisbourg
Université Lille-Nord de France, UDSL, Lille, France; Inserm U837, Jean-Pierre Aubert Research Centre, IMPRT, Lille France.
Antoine
A
Leboucher
Université Lille-Nord de France, UDSL, Lille, France; Inserm U837, Jean-Pierre Aubert Research Centre, IMPRT, Lille France.
Dominique
D
Demeyer
Université Lille-Nord de France, UDSL, Lille, France; Inserm U837, Jean-Pierre Aubert Research Centre, IMPRT, Lille France.
Sébastien
S
Carrier
PharmaCenter Bonn, Pharmaceutical Institute, University of Bonn, Bonn, Germany.
Marion
M
Schneider
Université Lille-Nord de France, UDSL, Lille, France; Inserm U837, Jean-Pierre Aubert Research Centre, IMPRT, Lille France.
Malika
M
Hamdane
PharmaCenter Bonn, Pharmaceutical Institute, University of Bonn, Bonn, Germany.
Christa E
CE
Müller
Université Lille-Nord de France, UDSL, Lille, France; Inserm U837, Jean-Pierre Aubert Research Centre, IMPRT, Lille France; CHRU-Lille, Lille France.
Luc
L
Buée
Université Lille-Nord de France, UDSL, Lille, France; Inserm U837, Jean-Pierre Aubert Research Centre, IMPRT, Lille France; CHRU-Lille, Lille France. Electronic address: david.blum@inserm.fr.
David
D
Blum
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D002110:Caffeine / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008569:Memory Disorders / Q000517:prevention & control; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins; D002110:Caffeine
Alzheimer's disease; Caffeine; Caffeine metabolites; THY-Tau22; Tau; Transgenic