Unidad de Neuroinflamación, Instituto de Investigaciones Biomédicas- Universidad Nacional Autónoma de México (UNAM) / Facultad de Medicina-UNAM/ Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, Mexico.
Clínica de Parkinson, Instituto Nacional de Neurología y Neurocirugía, Secretaría de Salud, Ciudad de México, Mexico.
Neurologia (Engl Ed). 2022 Mar;37(2):110-121. doi: 10.1016/j.nrleng.2018.10.022. Epub 2021 Feb 12.
Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis.
To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression.
The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales.
Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38+ in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases.
This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.
神经炎症参与了各种神经紊乱疾病的病理生理学过程,尤其是阿尔茨海默病(AD)和帕金森病(PD)。血脑屏障的改变可能会使外周血淋巴细胞进入中枢神经系统;这些细胞可能参与了疾病的发病机制。
评估 AD 和 PD 患者的外周血淋巴细胞谱及其与疾病和疾病进展的关系。
该研究纳入了 20 例 AD 患者、20 例 PD 患者和一组健康对照者。其中 10 例 AD 患者和 12 例 PD 患者在研究开始后 17-27 个月时进行了第二次评估。通过流式细胞术测定淋巴细胞亚群及其激活状态。所有患者均采用国际公认的量表进行神经学检查。
与健康对照者相比,AD 和 PD 患者的激活淋巴细胞、凋亡敏感淋巴细胞、中央记忆 T 细胞以及调节性 T 细胞和 B 细胞的水平显著更高。随着疾病的进展,激活细胞(PD 中的 CD4+ CD38+和 CD8+ CD38+,AD 中的 CD4+ CD69+和 CD8+ CD69+)、凋亡敏感 T 细胞以及一些调节性群体(PD 中的 CD19+ CD5+ IL10+和 AD 中的 CD19+ CD5+ IL10+ FoxP3+,PD 中的 CD4+ FoxP3+ CD25+ CD45RO+)的水平显著下降。在 AD 患者中,疾病进展与研究开始时较低的 CD4+ CD38+细胞比例和较高的效应 CD4 细胞比例相关。两种疾病之间存在显著差异。
本研究提供了与 AD 和 PD 及其严重程度相关的外周血淋巴细胞表型变化的证据。考虑到有效的血脑通讯,我们的结果为治疗这些疾病的免疫调节治疗开辟了新的研究途径。