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Title: 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
Authors: Duarte, Ana I. 
Candeias, Emanuel 
Alves, Inês 
Mena, Débora 
Silva, Daniela F. 
Machado, Nuno J. 
Campos, Elisa J. 
Santos, Maria S. 
Oliveira, Catarina R. 
Moreira, Paula I. 
Keywords: Alzheimer’s disease; brain protection; female sex; GLP-1 mimetics; liraglutide
Issue Date: 4-Mar-2020
Publisher: MDPI
Project: Centro-01-0145-FEDER-000012 
Post-Doctoral Researcher Contract DL57/2016 #SFRH/BPD/84473/2012 
Serial title, monograph or event: International Journal of Molecular Sciences
Volume: 21
Issue: 5
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, oxidative/nitrosative stress and inflammation in these AD female mice. Our results support the earlier use of liraglutide as a potential preventive/therapeutic agent against the accumulation of the first neuropathological features of AD in females.
ISSN: 1422-0067
DOI: 10.3390/ijms21051746
Rights: openAccess
Appears in Collections:IIIUC - Artigos em Revistas Internacionais
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FMUC Medicina - Artigos em Revistas Internacionais
I&D CIBB - Artigos em Revistas Internacionais

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