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Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease.
Neuropharmacology. 2014 Jan; 76 Pt A:57-67.N

Abstract

Type 2 diabetes is a risk factor in the development of Alzheimer's disease (AD). It has been shown that insulin signalling is desensitised in the brains of AD patients. The incretin hormone Glucagon-like peptide-1 (GLP-1) facilitates insulin signalling, and long-lasting analogues such as liraglutide (Victoza(®)) are on the market as type 2 diabetes treatments. We have previously shown that liraglutide improved cognitive function, reduced amyloid plaque deposition, inflammation, overall APP and oligomer levels and enhanced LTP when injected peripherally for two months in 7 month old APPswe/PS1ΔE9 (APP/PS1) mice. This showed that liraglutide has preventive effects at the early stage of AD development. The current study investigated whether Liraglutide would have restorative effects in late-stage Alzheimer's disease in mice. Accordingly, 14-month-old APP/PS1 and littermate control mice were injected with Liraglutide (25 nmol/kg bw) ip. for 2 months. Spatial memory was improved by Liraglutide-treatment in APP/PS1 mice compared with APP/PS1 saline-treated mice. Overall plaque load was reduced by 33%, and inflammation reduced by 30%, while neuronal progenitor cell count in the dentate gyrus was increased by 50%. LTP was significantly enhanced in APP/PS1 liraglutide-treated mice compared with APP/PS1 saline mice, corroborated with increased synapse numbers in hippocampus and cortex. Total brain APP and beta-amyloid oligomer levels were reduced in Liraglutide-treated APP/PS1 mice while IDE levels were increased. These results demonstrate that Liraglutide not only has preventive properties, but also can reverse some of the key pathological hallmarks of AD. Liraglutide is now being tested in clinical trials in AD patients. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.

Authors+Show Affiliations

School of Biomedical Sciences, University of Ulster, Cromore Road, Coleraine, BT52 1SA Northern Ireland, UK.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23973293

Citation

McClean, Paula L., and Christian Hölscher. "Liraglutide Can Reverse Memory Impairment, Synaptic Loss and Reduce Plaque Load in Aged APP/PS1 Mice, a Model of Alzheimer's Disease." Neuropharmacology, vol. 76 Pt A, 2014, pp. 57-67.
McClean PL, Hölscher C. Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease. Neuropharmacology. 2014;76 Pt A:57-67.
McClean, P. L., & Hölscher, C. (2014). Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease. Neuropharmacology, 76 Pt A, 57-67. https://doi.org/10.1016/j.neuropharm.2013.08.005
McClean PL, Hölscher C. Liraglutide Can Reverse Memory Impairment, Synaptic Loss and Reduce Plaque Load in Aged APP/PS1 Mice, a Model of Alzheimer's Disease. Neuropharmacology. 2014;76 Pt A:57-67. PubMed PMID: 23973293.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease. AU - McClean,Paula L, AU - Hölscher,Christian, Y1 - 2013/08/21/ PY - 2013/01/15/received PY - 2013/08/06/revised PY - 2013/08/08/accepted PY - 2013/8/27/entrez PY - 2013/8/27/pubmed PY - 2014/6/6/medline KW - Cognition KW - GLP-1 KW - Incretins KW - Inflammation KW - Insulin KW - Memory KW - Neurodegeneration KW - Neuroprotection KW - Stem cells KW - Synapse SP - 57 EP - 67 JF - Neuropharmacology JO - Neuropharmacology VL - 76 Pt A N2 - Type 2 diabetes is a risk factor in the development of Alzheimer's disease (AD). It has been shown that insulin signalling is desensitised in the brains of AD patients. The incretin hormone Glucagon-like peptide-1 (GLP-1) facilitates insulin signalling, and long-lasting analogues such as liraglutide (Victoza(®)) are on the market as type 2 diabetes treatments. We have previously shown that liraglutide improved cognitive function, reduced amyloid plaque deposition, inflammation, overall APP and oligomer levels and enhanced LTP when injected peripherally for two months in 7 month old APPswe/PS1ΔE9 (APP/PS1) mice. This showed that liraglutide has preventive effects at the early stage of AD development. The current study investigated whether Liraglutide would have restorative effects in late-stage Alzheimer's disease in mice. Accordingly, 14-month-old APP/PS1 and littermate control mice were injected with Liraglutide (25 nmol/kg bw) ip. for 2 months. Spatial memory was improved by Liraglutide-treatment in APP/PS1 mice compared with APP/PS1 saline-treated mice. Overall plaque load was reduced by 33%, and inflammation reduced by 30%, while neuronal progenitor cell count in the dentate gyrus was increased by 50%. LTP was significantly enhanced in APP/PS1 liraglutide-treated mice compared with APP/PS1 saline mice, corroborated with increased synapse numbers in hippocampus and cortex. Total brain APP and beta-amyloid oligomer levels were reduced in Liraglutide-treated APP/PS1 mice while IDE levels were increased. These results demonstrate that Liraglutide not only has preventive properties, but also can reverse some of the key pathological hallmarks of AD. Liraglutide is now being tested in clinical trials in AD patients. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/23973293/Liraglutide_can_reverse_memory_impairment_synaptic_loss_and_reduce_plaque_load_in_aged_APP/PS1_mice_a_model_of_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(13)00362-6 DB - PRIME DP - Unbound Medicine ER -