Treatment with glatiramer acetate in APPswe/PS1dE9 mice at an early stage of Alzheimer's disease prior to amyloid-beta deposition delays the disease's pathological development and ameliorates cognitive decline.

Background: Alzheimer's disease (AD) is characterized by neuroinflammation, which is frequently accompanied by immune system dysfunction. Although the mechanism of neurodegenerative lesions is unclear, various clinical trials have highlighted that early intervention in AD is crucial to the success of treatment. In order to explore the potential of immunotherapy in the early period of AD, the present study evaluated whether application of glatiramer acetate (GA), an immunomodulatory agent approved for remitting-relapsing multiple sclerosis (RRMS), in the early stages of AD prior to amyloid beta (Aß) deposition altered the Aß pathology and cognitive impairments in APPswe/PSEN1dE9 (APP/PS1) transgenic mice. Methods: We treated two cohorts of pre-depositing and amyloid-depositing (2- and 6-month-old) APP/PS1 mice with weekly-GA subcutaneous injection over a 12-week period. We then tested spatial learning and memory using the Morris water maze (MWM) and the Y maze. Immunohistochemistry staining was utilized to analyze Aß burden in the brain as well as activated microglia. Furthermore, the inflammatory cytokine milieu within brains was estimated by quantitative real-time polymerase chain reaction, and the peripheral CD4+CD25+Foxp3+ regulatory T cells (Tregs) in the spleen were measured by flow cytometry. Results: We found that early GA administration reduced Aß burden and ameliorated cognitive decline. Meanwhile, the immune microenvironment had changed in the brain, with an increase in the production of anti-inflammatory cytokines and a decrease in microglial activation. Interestingly, early GA administration also modulated the peripheral immune system through the amplification of Tregs in the spleen. Conclusion: Overall, our findings revealed that GA treatment might enhance the central and peripheral immune systems' protective capabilities in the early stages of AD, eventually improving cognitive deficits. Our research supports the advantages of immunomodulatory treatments for AD at an early stage.

Mild Cognitive Impairment Patients Have Higher Regulatory T-Cell Proportions Compared With Alzheimer's Disease-Related Dementia Patients.

Objectives: The role of neuroinflammation in the pathogenesis of Alzheimer's disease (AD) has attracted much attention recently. Regulatory T-cells (Tregs) play an important role in modulating inflammation. We aimed to explore the Treg-related immunosuppression status at different stages of AD. Methods: Thirty healthy control (HC) subjects, 26 patients with mild cognitive impairment (MCI), 30 patients with mild probable AD-related dementia, and 28 patients with moderate-to-severe probable AD-related dementia underwent detailed clinical history taking, structural MRI scanning, and neuropsychological assessment. Peripheral blood samples were taken to measure the percentage of CD4+CD25+CD127low/- Tregs by flow cytometry and the levels of interleukin (IL-10), interleukin (IL-35), and transforming growth factor ß (TGF-ß) by ELISA. Results: The percentage of Tregs in the blood of MCI patients was the highest (9.24%); there was a significant difference between patients with MCI and patients with probable AD-related dementia. The level of TGF-ß in patients with MCI (47.02 ng/ml) was significantly increased compared with patients with AD-related dementia. There were positive correlations between Treg percentage, IL-35, and Mini-mental state evaluation scores in patients with MCI and probable AD-related dementia. Conclusions: Patients with MCI have stronger Treg-related immunosuppression status compared with patients with probable AD-related dementia.