Cognition and Brain Integration Laboratory, Neurosciences Department, Huntington Medical Research Institutes, Pasadena, CA 91105, USA.
Biomarker and Neuro-Disease Mechanism Laboratory, Neurosciences Department, Huntington Medical Research Institutes, Pasadena, CA 91105, USA.
Cells. 2024 Jun 4;13(11):970. doi: 10.3390/cells13110970.
Electroencephalogram (EEG) studies have suggested compensatory brain overactivation in cognitively healthy (CH) older adults with pathological beta-amyloid(Aβ)/tau ratios during working memory and interference processing. However, the association between glutamatergic metabolites and brain activation proxied by EEG signals has not been thoroughly investigated. We aim to determine the involvement of these metabolites in EEG signaling. We focused on CH older adults classified under (1) normal CSF Aβ/tau ratios (CH-NATs) and (2) pathological Aβ/tau ratios (CH-PATs). We measured plasma glutamine, glutamate, pyroglutamate, and γ-aminobutyric acid concentrations using tandem mass spectrometry and conducted a correlational analysis with alpha frequency event-related desynchronization (ERD). Under the N-back working memory paradigm, CH-NATs presented negative correlations (r = ~-0.74--0.96, = 0.0001-0.0414) between pyroglutamate and alpha ERD but positive correlations (r = ~0.82-0.95, = 0.0003-0.0119) between glutamine and alpha ERD. Under Stroop interference testing, CH-NATs generated negative correlations between glutamine and left temporal alpha ERD (r = -0.96, = 0.037 and r = -0.97, = 0.027). Our study demonstrated that glutamine and pyroglutamate levels were associated with EEG activity only in CH-NATs. These results suggest cognitively healthy adults with amyloid/tau pathology experience subtle metabolic dysfunction that may influence EEG signaling during cognitive challenge. A longitudinal follow-up study with a larger sample size is needed to validate these pilot studies.
脑电图（EEG）研究表明，在工作记忆和干扰处理过程中，认知健康（CH）的老年个体中存在病理性β-淀粉样蛋白（Aβ）/tau 比值的大脑过度激活。然而，尚不清楚谷氨酸代谢物与 EEG 信号所代表的大脑激活之间的关联。我们旨在确定这些代谢物在 EEG 信号中的作用。我们专注于 CH 老年个体，他们被分为以下两类：（1）正常脑脊液 Aβ/tau 比值（CH-NATs）和（2）病理性 Aβ/tau 比值（CH-PATs）。我们使用串联质谱法测量了血浆谷氨酰胺、谷氨酸、焦谷氨酸和γ-氨基丁酸的浓度，并进行了与 alpha 频率事件相关去同步（ERD）的相关分析。在 N-back 工作记忆范式下，CH-NATs 表现出焦谷氨酸与 alpha ERD 之间的负相关（r = ~-0.74--0.96， = 0.0001-0.0414），而谷氨酰胺与 alpha ERD 之间的正相关（r = ~0.82-0.95， = 0.0003-0.0119）。在 Stroop 干扰测试中，CH-NATs 产生了谷氨酰胺与左侧颞部 alpha ERD 之间的负相关（r = -0.96， = 0.037 和 r = -0.97， = 0.027）。我们的研究表明，只有在 CH-NATs 中，谷氨酰胺和焦谷氨酸的水平与 EEG 活动相关。这些结果表明，具有淀粉样蛋白/tau 病理学的认知健康成年人经历了微妙的代谢功能障碍，这可能会影响认知挑战期间的 EEG 信号。需要进行更大样本量的纵向随访研究来验证这些初步研究。
