Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - The diabetes drug Liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease
AU - McClean, Paula L.
AU - Parthsarathy, Vadivel
AU - Faivre, Emilie
AU - Holscher, Christian
PY - 2011/4/27
Y1 - 2011/4/27
N2 - Type 2 diabetes is a risk factor for Alzheimer's disease, most likely linked to an impairment of insulin signaling in the brain. The incretin hormone glucagon-like peptide-1 (GLP-1) facilitates insulin signaling, and novel long-lasting GLP-1 analogs, such as liraglutide, are on the market as diabetes therapeutics. GLP-1 has been shown to have neuroprotective properties in vitro and in vivo. Here we tested the effects of peripherally injected liraglutide in an Alzheimer mouse model, APPswe/PS1ΔE9 (APP/PS1). Liraglutide was shown to cross the blood–brain barrier in an acute study. Liraglutide was injected for 8 weeks at 25 nmol/kg body weight i.p. once daily in 7-month-old APP/PS1 and wild-type littermate controls. In APP/PS1 mice, liraglutide prevented memory impairments in object recognition and water maze tasks, and prevented synapse loss and deterioration of synaptic plasticity in the hippocampus, commonly observed in this model. Overall β-amyloid plaque count in the cortex and dense-core plaque numbers were reduced by 40–50%, while levels of soluble amyloid oligomers were reduced by 25%. The inflammation response as measured by activated microglia numbers was halved in liraglutide-treated APP/PS1 mice. Numbers of young neurons in the dentate gyrus were increased in APP/PS1 mice with treatment. Liraglutide treatment had little effect on littermate control mice, whose behavior was comparable to wild-type saline controls; however, synaptic plasticity was enhanced in the drug group. Our results show that liraglutide prevents key neurodegenerative developments found in Alzheimer's disease, suggesting that GLP-1 analogs represent a novel treatment strategy for Alzheimer's disease.
AB - Type 2 diabetes is a risk factor for Alzheimer's disease, most likely linked to an impairment of insulin signaling in the brain. The incretin hormone glucagon-like peptide-1 (GLP-1) facilitates insulin signaling, and novel long-lasting GLP-1 analogs, such as liraglutide, are on the market as diabetes therapeutics. GLP-1 has been shown to have neuroprotective properties in vitro and in vivo. Here we tested the effects of peripherally injected liraglutide in an Alzheimer mouse model, APPswe/PS1ΔE9 (APP/PS1). Liraglutide was shown to cross the blood–brain barrier in an acute study. Liraglutide was injected for 8 weeks at 25 nmol/kg body weight i.p. once daily in 7-month-old APP/PS1 and wild-type littermate controls. In APP/PS1 mice, liraglutide prevented memory impairments in object recognition and water maze tasks, and prevented synapse loss and deterioration of synaptic plasticity in the hippocampus, commonly observed in this model. Overall β-amyloid plaque count in the cortex and dense-core plaque numbers were reduced by 40–50%, while levels of soluble amyloid oligomers were reduced by 25%. The inflammation response as measured by activated microglia numbers was halved in liraglutide-treated APP/PS1 mice. Numbers of young neurons in the dentate gyrus were increased in APP/PS1 mice with treatment. Liraglutide treatment had little effect on littermate control mice, whose behavior was comparable to wild-type saline controls; however, synaptic plasticity was enhanced in the drug group. Our results show that liraglutide prevents key neurodegenerative developments found in Alzheimer's disease, suggesting that GLP-1 analogs represent a novel treatment strategy for Alzheimer's disease.
UR - http://www.scopus.com/inward/record.url?scp=79955749452&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0529-11.2011
DO - 10.1523/JNEUROSCI.0529-11.2011
M3 - Journal article
AN - SCOPUS:79955749452
VL - 31
SP - 6587
EP - 6594
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 17
ER -