Global aging has led to growing health concerns posed by Alzheimer’s disease (AD), the most common type of dementia. Aripiprazole is an atypical FDA-approved anti-psychotic drug with potential against AD. To investigate its therapeutic effects on AD pathology, we administered aripiprazole to 5xFAD AD model mice and examined beta-amyloid (βA)-induced AD-like phenotypes, including βA production, neuroinflammation, and cerebral glucose metabolism. Aripiprazole administration significantly decreased βA accumulation in the brains of 5xFAD AD mice. Aripiprazole significantly modified amyloid precursor protein processing, including carboxyl-terminal fragment β and βA, a disintegrin and metalloproteinase domain-containing protein 10, and betasite APP cleaving enzyme 1, as determined by Western blotting. Neuroinflammation, as evidenced by ionized calcium binding adapter molecule 1 and glial fibrillary acidic protein upregulation was dramatically inhibited, and the neuron cell layer of the hippocampal CA1 region was preserved following aripiprazole administration. In 18F-fluorodeoxyglucose positron emission tomography, after receiving aripiprazole, 5xFAD mice showed a significant increase in glucose uptake in the striatum, thalamus, and hippocampus compared to vehicle-treated AD mice. Thus, aripiprazole effectively alleviated βA lesions and prevented the decline of cerebral glucose metabolism in 5xFAD AD mice, suggesting its potential for βA metabolic modification and highlighting its therapeutic effect over AD progression.
Bibliographical noteFunding Information:
Funding: This work was supported by a grant of the Korea Institute of Radiological and Medical Sciences (No. 50531-2021) and the National Research Foundation of Korea (NRF-2020R1C1C1006659) funded by the Korean government Ministry of Science and ICT (MSIT).
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- Alzheimer’s disease mice
- Therapeutic agent
- βA pathology
ASJC Scopus subject areas
- Molecular Biology
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry