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Licensed Unlicensed Requires Authentication Published by De Gruyter November 21, 2013

New animal models of Alzheimer’s disease that display insulin desensitization in the brain

  • Chong Gao

    Gao Chong obtained his Master of Science from Shanxi Medical university. His research direction is now on the cognitive function of human brain, pathological mechanisms of neurodegenerative diseases, and the therapeutic effects of anti-diabetic agents to treat neurodegeneration.

    , Yueze Liu

    Professor Yue-Ze Liu, PhD, was born in 1957. She is President of third hospital, Shanxi Medical University. She has focused her research interests on health technique assessment. She is particularly interested in assessing the effects of GLP-1 analogs in clinic trials.

    , Lin Li

    Professor Lin Li, PhD was born in 1957. He has focused his research interests on biological investigations on how to prevent or delay Alzheimer’s disease, especially in relation to the protective effects of GLP-1.

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    and Christian Hölscher

    Christian Hölscher is Professor of Neuroscience at the University of Lancaster, England. His group is involved in the development of novel drug treatments for Alzheimer’s and Parkinson’s disease. His research focus is on the interaction between diabetes and neurodegeneration, which led him to discover the neuroprotective properties of incretin analogues which are currently on the market to treat type 2 diabetes. One of the drugs profiled by him is now in clinical trials in patients with Alzheimer’s disease. Further trials in patients with Parkinson’s disease are in planning.

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Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative disorder, which involves many underlying pathological processes. Recently, it has been demonstrated that AD also includes impairments of insulin signaling in the brain. Type 2 diabetes is a risk factor for AD, and AD and diabetes share a number of pathologies. The classical hallmarks of AD are senile plaques and neurofibrillary tangles, which consist of amyloid-β and hyperphosphorylated tau. Based on the two hallmarks, transgenic animal models of AD have been developed, which express mutant human genes of amyloid precursor protein, presenilin-1/2, and tau. It is likely that these mouse models are too limited in their pathology. In this work, we describe mouse models that model diabetes and show insulin signaling impairment as well as neurodegenerative pathologies that are similar to those seen in the brains of AD patients. The combination of traditional AD mouse models with induced insulin impairments in the brain may be a more complete model of AD. Interestingly, AD mouse models treated with drugs that have been developed to cure type 2 diabetes have shown impressive outcomes. Based on these findings, several ongoing clinical trials are testing long lasting insulin analogues or GLP-1 mimetics in patients with AD.


Corresponding authors: Lin Li, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 300001, PR China, e-mail: ; and Christian Hölscher, Division of Biomedical and Life Sciences, Lancaster University, Lancaster LA1 4YQ, UK; and Second Hospital, Shanxi Medical University, Taiyuan 300002, PR China, e-mail:

About the authors

Chong Gao

Gao Chong obtained his Master of Science from Shanxi Medical university. His research direction is now on the cognitive function of human brain, pathological mechanisms of neurodegenerative diseases, and the therapeutic effects of anti-diabetic agents to treat neurodegeneration.

Yueze Liu

Professor Yue-Ze Liu, PhD, was born in 1957. She is President of third hospital, Shanxi Medical University. She has focused her research interests on health technique assessment. She is particularly interested in assessing the effects of GLP-1 analogs in clinic trials.

Lin Li

Professor Lin Li, PhD was born in 1957. He has focused his research interests on biological investigations on how to prevent or delay Alzheimer’s disease, especially in relation to the protective effects of GLP-1.

Christian Hölscher

Christian Hölscher is Professor of Neuroscience at the University of Lancaster, England. His group is involved in the development of novel drug treatments for Alzheimer’s and Parkinson’s disease. His research focus is on the interaction between diabetes and neurodegeneration, which led him to discover the neuroprotective properties of incretin analogues which are currently on the market to treat type 2 diabetes. One of the drugs profiled by him is now in clinical trials in patients with Alzheimer’s disease. Further trials in patients with Parkinson’s disease are in planning.

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Received: 2013-8-10
Accepted: 2013-9-29
Published Online: 2013-11-21
Published in Print: 2013-12-01

©2013 by Walter de Gruyter Berlin Boston

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