The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide are neuroprotective in mouse models of Alzheimer's disease

Biomedical and Life Sciences

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https://doi.org/10.1016/j.jalz.2013.12.009
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Keywords

Alzheimer's disease, Parkinson's disease , Growth factors , GLP-1 , Liraglutide , Lixisenatide

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The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide are neuroprotective in mouse models of Alzheimer's disease. / Hölscher, Christian.
In: Alzheimer's and Dementia, Vol. 10, No. 1 Supplement, 02.2014, p. S47-54.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Bibtex

@article{e7d458720f6a4fa6875b084766a564c8,

title = "The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide are neuroprotective in mouse models of Alzheimer's disease",

abstract = "The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide (GIP) have been developed to treat type 2 diabetes and also act as growth factors. We have tested several long-acting incretin mimetics in the amyloid precursor protein (APP)(Swe)/presenilin 1 (PS1)(ΔE9) model of Alzheimer's disease (AD). We found that liraglutide, lixisenatide, and D-Ala2-GIP cross the blood-brain barrier and prevent the impairment in memory formation and synaptic plasticity, increase synapse numbers, reduce amyloid plaque load and soluble amyloid-β levels, reduce oxidative stress and the chronic inflammation response in the brain, enhance the proliferation of neuronal progenitor cells, and increase neurogenesis in the dentate gyrus. In an (18)fluorodeoxyglucoe positron emission tomographic/computed tomographic imaging study in PLB1-triple mice, a mouse model that expresses human mutated APP, PS1, and tau proteins, glucose metabolism was found to be normalized in forebrain areas after liraglutide treatment, demonstrating that neuronal metabolic activity was normalized. A clinical trial testing liraglutide in patients with AD is currently ongoing.",

keywords = "Alzheimer's disease, Parkinson's disease , Growth factors , GLP-1 , Liraglutide , Lixisenatide",

author = "Christian H{\"o}lscher",

year = "2014",

month = feb,

doi = "10.1016/j.jalz.2013.12.009",

language = "English",

volume = "10",

pages = "S47--54",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Wiley",

number = "1 Supplement",

}

RIS

TY - JOUR

T1 - The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide are neuroprotective in mouse models of Alzheimer's disease

AU - Hölscher, Christian

PY - 2014/2

Y1 - 2014/2

N2 - The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide (GIP) have been developed to treat type 2 diabetes and also act as growth factors. We have tested several long-acting incretin mimetics in the amyloid precursor protein (APP)(Swe)/presenilin 1 (PS1)(ΔE9) model of Alzheimer's disease (AD). We found that liraglutide, lixisenatide, and D-Ala2-GIP cross the blood-brain barrier and prevent the impairment in memory formation and synaptic plasticity, increase synapse numbers, reduce amyloid plaque load and soluble amyloid-β levels, reduce oxidative stress and the chronic inflammation response in the brain, enhance the proliferation of neuronal progenitor cells, and increase neurogenesis in the dentate gyrus. In an (18)fluorodeoxyglucoe positron emission tomographic/computed tomographic imaging study in PLB1-triple mice, a mouse model that expresses human mutated APP, PS1, and tau proteins, glucose metabolism was found to be normalized in forebrain areas after liraglutide treatment, demonstrating that neuronal metabolic activity was normalized. A clinical trial testing liraglutide in patients with AD is currently ongoing.

AB - The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide (GIP) have been developed to treat type 2 diabetes and also act as growth factors. We have tested several long-acting incretin mimetics in the amyloid precursor protein (APP)(Swe)/presenilin 1 (PS1)(ΔE9) model of Alzheimer's disease (AD). We found that liraglutide, lixisenatide, and D-Ala2-GIP cross the blood-brain barrier and prevent the impairment in memory formation and synaptic plasticity, increase synapse numbers, reduce amyloid plaque load and soluble amyloid-β levels, reduce oxidative stress and the chronic inflammation response in the brain, enhance the proliferation of neuronal progenitor cells, and increase neurogenesis in the dentate gyrus. In an (18)fluorodeoxyglucoe positron emission tomographic/computed tomographic imaging study in PLB1-triple mice, a mouse model that expresses human mutated APP, PS1, and tau proteins, glucose metabolism was found to be normalized in forebrain areas after liraglutide treatment, demonstrating that neuronal metabolic activity was normalized. A clinical trial testing liraglutide in patients with AD is currently ongoing.

KW - Alzheimer's disease

KW - Parkinson's disease

KW - Growth factors

KW - GLP-1

KW - Liraglutide

KW - Lixisenatide

U2 - 10.1016/j.jalz.2013.12.009

DO - 10.1016/j.jalz.2013.12.009

M3 - Journal article

C2 - 24529525

VL - 10

SP - S47-54

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

SN - 1552-5260

IS - 1 Supplement

ER -

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