Wang Meng-Ting, Wang Ye-Ran, Zeng Gui-Hua, Zeng Xiao-Qin, Fei Zhang-Cheng, Chen Jia, Zhou Jin, Li Xin-Peng, Xu Zhi-Qiang, Wang Yan-Jiang, Liu Yu-Hui
Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, PR China.
Department of Rehabilitation, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. Postal address: 400010.
J Prev Alzheimers Dis. 2025 Aug;12(7):100135. doi: 10.1016/j.tjpad.2025.100135. Epub 2025 Mar 21.
Dysfunction of humoral immunity has been implicated in the pathogenesis of Alzheimer's disease (AD). The distribution of B lymphocyte subsets and their clinical relevance in AD remain unclear.
In this study, we aimed to investigate the distribution of peripheral blood B lymphocyte subsets and their relevance with cognition and biomarkers in AD.
DESIGN, SETTING, AND PARTICIPANTS: We evaluated the immunophenotype of peripheral B lymphocytes in 27 AD patients confirmed by PET-Amyloid scan and 32 cognitively normal controls.
The phenotype of B lymphocytes is altered in AD patients. AD patients exhibit a decrease in both the numbers and proportions of switched memory (SwM) B cells and double-negative (DN) B cells. The proportion of unswitched memory (USwM) B cells was increased after in vitro stimulation. Additionally, B cells that produce proinflammatory cytokines including GM-CSF, IFN-γ, and TNF-α are increased, while those that produce the anti-inflammatory cytokine IL-10 are decreased in AD patients after in vitro stimulation. These alterations in B cell populations were linked to cognitive functions and biomarkers, including Aβ42/40 and pTau181, in AD patients.
This study reveals an altered B-lymphocyte phenotype in AD patients, marked by functional and compositional dysregulation. Further research incorporating mechanistic, longitudinal, and functional studies is needed to determine whether these immune perturbations directly contribute to AD pathogenesis or arise as secondary effects of neurodegeneration.
体液免疫功能障碍与阿尔茨海默病（AD）的发病机制有关。AD中B淋巴细胞亚群的分布及其临床相关性尚不清楚。
在本研究中，我们旨在调查外周血B淋巴细胞亚群的分布及其与AD认知和生物标志物的相关性。
设计、设置和参与者：我们评估了27例经PET淀粉样蛋白扫描确诊的AD患者和32例认知正常对照者外周B淋巴细胞的免疫表型。
AD患者B淋巴细胞的表型发生改变。AD患者转换记忆（SwM）B细胞和双阴性（DN）B细胞的数量和比例均降低。体外刺激后未转换记忆（USwM）B细胞的比例增加。此外，体外刺激后，AD患者中产生促炎细胞因子（包括GM-CSF、IFN-γ和TNF-α）的B细胞增加，而产生抗炎细胞因子IL-10的B细胞减少。AD患者B细胞群体的这些改变与认知功能和生物标志物有关，包括Aβ42/40和pTau181。
本研究揭示了AD患者B淋巴细胞表型的改变，其特征是功能和组成失调。需要进一步开展机制、纵向和功能研究，以确定这些免疫紊乱是直接导致AD发病机制还是作为神经退行性变的继发效应出现。
