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GLP-1 receptor stimulation reduces amyloid-β peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer’s disease


Year of Publication:
Contact PI Name:
Nigel H. Greig
Contact PI Affiliation:
Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, Baltimore, Maryland, USA
Yazhou Li, Kara B. Duffy, Mary Ann Ottinger, Balmiki Ray, Jason A. Bailey, Harold W. Holloway, David Tweedie, TracyAnn Perry, Mark P. Mattson, Dimitrios Kapogiannis, Kumar Sambamurti, Debomoy K. Lahiri
Primary Reference (PubMED ID):
Funding Source:
Intramural Research Program of the National Institute on Aging
National Institute on Aging (NIA)
Medstar Research Institute
Study Goal and Principal Findings:

The  goal of this study present study was to characterize the effects, of a clinically approved  Type 2 diabetes drug, exendin-4 (Ex-4), an agonist of the of the glucagon-like peptide-1 receptor (GLP-1R), on stress-induced toxicity in neuronal cultures and on amyloid-β protein (Aβ) and tau levels in 3xTg-AD mouse model . 3xTg-AD mice were treated with streptozocin (STZ) to model diabetes. 3xTg-AD mice treated with saline instead of STZ served as controls. STZ 3xTg-AD mice were found to have elevated levels of APP and Aβ compared to saline treated mice. STZ treatment of Tg mice did not affect tau levels significantly. Compared to vehicle Ex-4 treatment ameliorated the diabetic effects of STZ in Tg mice, as measured by elevated plasma insulin and lowered plasma glucose and hemoglobin A1c (HbA1c) levels. In addition, Ex-4 treatment, compared to vehicle, ameliorated the STZ-induced increases in APP and Aβ. Ex-4 ameliorated the toxicity of Aβ and oxidative challenge in primary neuronal cultures and human SH-SY5Y cells in a concentration-dependent manner. Together, these results suggest that Ex-4 may have potential in treating AD alone or in association with Type 2 diabetes.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Peptide
Therapeutic Agent:
Therapeutic Target:
Glucagon-Like Peptide 1 Receptor (GLP-1R)

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Not Reported

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Brain-beta Amyloid Peptide-Total
Total Tau Protein
Amyloid Precursor Protein (APP)
Blood-Glucose Level
Tau Protein
Cell Biology
Neuroprotection-Amyloid Neurotoxicity