Liraglutide Protects Against Brain Amyloid-β1-42 Accumulation in Female Mice with Early Alzheimer's Disease-Like Pathology by Partially Rescuing Oxidative/Nitrosative Stress and Inflammation

International Journal of Molecular Sciences
Ana I DuartePaula I Moreira

Abstract

Alzheimer's disease (AD) is the most common form of dementia worldwide, being characterized by the deposition of senile plaques, neurofibrillary tangles (enriched in the amyloid beta (Aβ) peptide and hyperphosphorylated tau (p-tau), respectively) and memory loss. Aging, type 2 diabetes (T2D) and female sex (especially after menopause) are risk factors for AD, but their crosslinking mechanisms remain unclear. Most clinical trials targeting AD neuropathology failed and it remains incurable. However, evidence suggests that effective anti-T2D drugs, such as the GLP-1 mimetic and neuroprotector liraglutide, can be also efficient against AD. Thus, we aimed to study the benefits of a peripheral liraglutide treatment in AD female mice. We used blood and brain cortical lysates from 10-month-old 3xTg-AD female mice, treated for 28 days with liraglutide (0.2 mg/kg, once/day) to evaluate parameters affected in AD (e.g., Aβ and p-tau, motor and cognitive function, glucose metabolism, inflammation and oxidative/nitrosative stress). Despite the limited signs of cognitive changes in mature female mice, liraglutide only reduced their cortical Aβ1-42 levels. Liraglutide partially attenuated brain estradiol and GLP-1 and activated PKA levels, oxi...Continue Reading

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Citations

Jan 24, 2021·Molecular Neurobiology·Anit Tyagi, Subbiah Pugazhenthi
Apr 27, 2021·Expert Opinion on Investigational Drugs·Evans D PopeMarwan Noel Sabbagh
Oct 31, 2020·Life Sciences·Habib YaribeygiAmirhossein Sahebkar
Jun 14, 2021·Alzheimer's Research & Therapy·Maria Vargas-SoriaMonica Garcia-Alloza

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Methods Mentioned

BETA
transgenic
Assay
ELISA
blood collection
electrophoresis

Software Mentioned

ARRIVE
GraphPad Prism
SPSS
FELASA
QuantityOne
Power
GraphPad

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