Winford Edric, Lutshumba Jenny, Martin Barbara J, Wilcock Donna M, Jicha Gregory A, Nikolajczyk Barbara S, Stowe Ann M, Bachstetter Adam D
Department of Neuroscience, University of Kentucky, 741 S. Limestone St. Rm B459, Lexington, KY, 40536, USA.
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
Immun Ageing. 2024 Jun 12;21(1):36. doi: 10.1186/s12979-024-00443-2.
The immune response changes during aging and the progression of Alzheimer's disease (AD) and related dementia (ADRD). Terminally differentiated effector memory T cells (called T) are important during aging and AD due to their cytotoxic phenotype and association with cognitive decline. However, it is not clear if the changes seen in T are specific to AD-related cognitive decline specifically or are more generally correlated with cognitive decline. This study aimed to examine whether T are associated with cognition and plasma biomarkers of AD, neurodegeneration, and neuroinflammation in a community-based cohort of older adults.
Study participants from a University of Kentucky Alzheimer's Disease Research Center (UK-ADRC) community-based cohort of aging and dementia were used to test our hypothesis. There were 84 participants, 44 women and 40 men. Participants underwent physical examination, neurological examination, medical history, cognitive testing, and blood collection to determine plasma biomarker levels (Aβ42/Aβ40 ratio, total tau, Neurofilament Light chain (Nf-L), Glial Fibrillary Acidic Protein (GFAP)) and to isolate peripheral blood mononuclear cells (PBMCs). Flow cytometry was used to analyze PBMCs from study participants for effector and memory T cell populations, including CD4 and CD8 central memory T cells (T), Naïve T cells, effector memory T cells (T), and effector memory CD45RA T cells (T) immune cell markers.
CD8 T were positively correlated with Nf-L and GFAP. We found no significant difference in CD8 T based on cognitive scores and no associations between CD8 T and AD-related biomarkers. CD4 T were associated with cognitive impairment on the MMSE. Gender was not associated with T, but it did show an association with other T cell populations.
These findings suggest that the accumulation of CD8 T may be a response to neuronal injury (Nf-L) and neuroinflammation (GFAP) during aging or the progression of AD and ADRD. As our findings in a community-based cohort were not clinically-defined AD participants but included all ADRDs, this suggests that T may be associated with changes in systemic immune T cell subsets associated with the onset of pathology.
免疫反应在衰老以及阿尔茨海默病（AD）和相关痴呆症（ADRD）的进展过程中会发生变化。终末分化的效应记忆T细胞（称为T细胞）在衰老和AD过程中很重要，因为它们具有细胞毒性表型且与认知能力下降有关。然而，尚不清楚T细胞中观察到的变化是否特定于AD相关的认知能力下降，还是更普遍地与认知能力下降相关。本研究旨在调查在一个基于社区的老年人群队列中，T细胞是否与AD、神经退行性变和神经炎症的认知及血浆生物标志物相关。
来自肯塔基大学阿尔茨海默病研究中心（UK-ADRC）基于社区的衰老和痴呆症队列的研究参与者被用于检验我们的假设。共有84名参与者，44名女性和40名男性。参与者接受了体格检查、神经学检查、病史询问、认知测试以及血液采集，以确定血浆生物标志物水平（Aβ42/Aβ40比值、总tau蛋白、神经丝轻链（Nf-L）、胶质纤维酸性蛋白（GFAP））并分离外周血单个核细胞（PBMCs）。流式细胞术用于分析研究参与者的PBMCs中的效应和记忆T细胞群体，包括CD4和CD8中央记忆T细胞（T细胞）、初始T细胞、效应记忆T细胞（T细胞）以及效应记忆CD45RA T细胞（T细胞）免疫细胞标志物。
CD8 T细胞与Nf-L和GFAP呈正相关。我们发现基于认知分数的CD8 T细胞无显著差异，且CD8 T细胞与AD相关生物标志物之间无关联。CD4 T细胞与MMSE上的认知障碍相关。性别与T细胞无关，但与其他T细胞群体有关联。
这些发现表明，CD8 T细胞的积累可能是衰老或AD及ADRD进展过程中对神经元损伤（Nf-L）和神经炎症（GFAP）的一种反应。由于我们在基于社区的队列中的发现并非临床定义的AD参与者，而是包括了所有ADRD患者，这表明T细胞可能与病理发生相关的全身免疫T细胞亚群变化有关。
