title: Old age potentiates cold-induced tau phosphorylation: linking thermoregulatory deficit with Alzheimer's disease.
abstract: Thermoregulatory deficits coincide with a rise in the incidence of Alzheimer's disease (AD) in old age. Lower body temperature increases tau phosphorylation, a neuropathological hallmark of AD. To determine whether old age potentiates cold-induced tau phosphorylation, we compared the effects of cold exposure (4 °C, 24 hours) in 6- and 18-month-old mice. Cold-induced changes in body temperature, brown adipose tissue activity, and phosphorylation of tau at Ser202 were not different between 6- and 18-month-old mice. However, following cold exposure, only old mice displayed a significant rise in soluble tau pThr181 and pThr231, which was correlated with body temperature. Inactivation of glycogen synthase kinase 3β was more prominent in young mice, suggesting a protective mechanism against cold-induced tau phosphorylation. These results suggest that old age confers higher susceptibility to tau hyperphosphorylation following a change in body temperature, thereby contributing to an enhanced risk of developing AD.
authors.affiliation: Faculté de pharmacie, Université Laval, Québec, Québec, Canada; Axe Neurosciences, Centre de recherche du centre Hospitalier de l'Université Laval (CHUL), Québec, Québec, Canada; Institut sur la Nutrition et les Aliments Fonctionnels, Québec, Québec, Canada.
authors.forename: Marine
authors.initials: M
authors.lastname: Tournissac
authors.affiliation: Faculté de pharmacie, Université Laval, Québec, Québec, Canada; Axe Neurosciences, Centre de recherche du centre Hospitalier de l'Université Laval (CHUL), Québec, Québec, Canada; Institut sur la Nutrition et les Aliments Fonctionnels, Québec, Québec, Canada.
authors.forename: Milène
authors.initials: M
authors.lastname: Vandal
authors.affiliation: Faculté de pharmacie, Université Laval, Québec, Québec, Canada; Axe Neurosciences, Centre de recherche du centre Hospitalier de l'Université Laval (CHUL), Québec, Québec, Canada.
authors.forename: Arnaud
authors.initials: A
authors.lastname: François
authors.affiliation: Axe Neurosciences, Centre de recherche du centre Hospitalier de l'Université Laval (CHUL), Québec, Québec, Canada; Faculté de médecine, Département de psychiatrie et de neurosciences, Université Laval, Québec, Québec, Canada.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Planel
authors.affiliation: Faculté de pharmacie, Université Laval, Québec, Québec, Canada; Axe Neurosciences, Centre de recherche du centre Hospitalier de l'Université Laval (CHUL), Québec, Québec, Canada; Institut sur la Nutrition et les Aliments Fonctionnels, Québec, Québec, Canada. Electronic address: frederic.calon@crchul.ulaval.ca.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Calon
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000209:etiology* / Q000503:physiopathology*; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D001833:Body Temperature Regulation / Q000502:physiology*; D003080:Cold Temperature; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D000071679:Glycogen Synthase Kinase 3 beta
keywords: Aging; Alzheimer's disease; Body temperature; Tau; Thermoregulation