TY - JOUR
T1 - Long-term treatment with lithium alleviates memory deficits and reduces amyloid-β production in an aged Alzheimer's disease transgenic mouse model
AU - Zhang, Xin
AU - Heng, Xin
AU - Li, Ting
AU - Li, Lixi
AU - Yang, Dehua
AU - Zhang, Xiaojie
AU - Du, Yunlan
AU - Doody, Rachelle S.
AU - Le, Weidong
PY - 2011
Y1 - 2011
N2 - 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 (AβPP Swe/PS1 A246E). 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.
AB - 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 (AβPP Swe/PS1 A246E). 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.
KW - AβPP processing
KW - Alzheimer's disease
KW - autophagy
KW - GSK3β
KW - lithium chloriD.E.
KW - spatial learning and memory
UR - http://www.scopus.com/inward/record.url?scp=79959276349&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959276349&partnerID=8YFLogxK
U2 - 10.3233/JAD-2011-101875
DO - 10.3233/JAD-2011-101875
M3 - Article
C2 - 21321394
AN - SCOPUS:79959276349
VL - 24
SP - 739
EP - 749
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 4
ER -