journal articles
FINGOLIMOD AMELIORATES AMYLOID DEPOSITION AND NEURODEGENERATION IN APP/PS1 MOUSE MODEL OF ALZHEIMER\'S DISEASE
Meng-Ting Wang, Zi-Cheng Hu, Yang Xiang, Xiao-Qin Zeng, Zhang-Cheng Fei, Jia Chen, Xin-Peng Li, Yu-Peng Zhu, Jun Wang, Yan-Jiang Wang, Zhi-Qiang Xu, Yu-Hui Liu
INTRODUCTION: The immune system plays a critical role in regulating amyloid-beta (Aβ) metabolism in Alzheimer's Disease (AD). Both T and B lymphocytes are involved in the pathogenesis of AD. The sphingosine-1-phosphate (S1P) receptor modulator fingolimod used in the treatment of multiple sclerosis, can promote lymphocyte homing, potentially reducing the infiltration of peripheral lymphocytes into the brain.
METHODS: In this study, 8-month-old APP/PS1 mice were orally administered fingolimod at a dose of 1 mg/kg/day or saline as a control for 2 months. After treatment, the mice were subjected to behavioral tests, pathological examinations, and biochemical analyses to evaluate behavioral deficits and AD-type pathologies.
RESULTS: Fingolimod inhibits the infiltration of peripheral lymphocytes into the brain and reduces neuroinflammation. Fingolimod enhances cognitive function and alleviates brain Aβ deposition. Additionally, fingolimod treatment mitigates other AD-related pathologies, including Tau hyperphosphorylation, neuroinflammation, and neurodegeneration. Proteomic analysis further confirms the therapeutic effects of fingolimod in AD, reflected by the downregulation of proteins involved in multiple AD-associated pathways.
DiISCUSSION: This study illustrates that fingolimod effectively ameliorates multiple pathological features of AD, highlighting its potential as a promising therapeutic candidate for the disease.
CITATION:
Meng-Ting Wang ; Zi-Cheng Hu ; Yang Xiang ; Xiao-Qin Zeng ; Zhang-Cheng Fei ; Jia Chen ; Xin-Peng Li ; Yu-Peng Zhu ; Jun Wang ; Yan-Jiang Wang ; Zhi-Qiang Xu ; Yu-Hui Liu (2025): Fingolimod ameliorates amyloid deposition and neurodegeneration in APP/PS1 mouse model of Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100131