title: Long-term treatment with lithium alleviates memory deficits and reduces amyloid-β production in an aged Alzheimer's disease transgenic mouse model.
abstract: The glycogen synthase kinase-3β (GSK3β) pathway plays a central role in Alzheimer's disease (AD) and its deregulation accounts for many of the pathological hallmarks of AD. Lithium, which modulates GSK3β activity, has been shown to reduce amyloid production and tau phosphorylation in pre-pathological AD mouse models. In this study, we investigated the effects of chronic LiCl treatment in aged double transgenic mice (AβPPSwe/PS1A246E). We found that chronic lithium treatment decreased the γ-cleavage of amyloid-β protein precursor, further reduced amyloid-β production and senile plaque formation, accompanied by the improvement in spatial learning and memory abilities. Because autophagy may play an important role in the pathology of AD, we also assessed the autophagy activity and found that the chronic lithium treatment attenuated the autophagy activation in this AD mouse model. Our results suggest that prolonged lithium treatment, even during the later stages of AD, could be an effective therapeutics.
authors.affiliation: Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Heng
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Lixi
authors.initials: L
authors.lastname: Li
authors.forename: Dehua
authors.initials: D
authors.lastname: Yang
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Zhang
authors.forename: Yunlan
authors.initials: Y
authors.lastname: Du
authors.forename: Rachelle S
authors.initials: RS
authors.lastname: Doody
authors.forename: Weidong
authors.initials: W
authors.lastname: Le
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics / Q000473:pathology; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology / Q000627:therapeutic use*; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016229:Amyloid beta-Peptides; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride