Schreiner Simon J, Van Bergen Jiri M G, Gietl Anton F, Buck Alfred, Hock Christoph, Pruessmann Klaas P, Henning Anke, Unschuld Paul G
Institute for Regenerative Medicine University of Zurich Zurich Switzerland.
Department of Psychogeriatric Medicine Psychiatric University Hospital Zurich (PUK) Zurich Switzerland.
Alzheimers Dement (Amst). 2024 Apr 30;16(2):e12587. doi: 10.1002/dad2.12587. eCollection 2024 Apr-Jun.
Gamma-hydroxy-butyric acid (GABA) and glutamate are neurotransmitters with essential importance for cognitive processing. Here, we investigate relationships between GABA, glutamate, and brain ß-amyloid (Aß) burden before clinical manifestation of Alzheimer's disease (AD). Thirty cognitively healthy adults (age 69.9 ± 6 years) received high-resolution atlas-based H-magnetic resonance spectroscopic imaging (MRSI) at ultra-high magnetic field strength of 7 Tesla for gray matter-specific assessment of GABA and glutamate. We assessed Aß burden with positron emission tomography and risk factors for AD. Higher gray matter GABA and glutamate related to higher Aß-burden (= 0.60, < 0.05; = 0.64, < 0.02), with positive effect modification by apolipoprotein-E-epsilon-4-allele (APOE4) ( = 0.01-0.03). GABA and glutamate negatively related to longitudinal change in verbal episodic memory performance (= -0.48; = 0.02; = -0.50; = 0.01). In vivo measures of GABA and glutamate reflect early AD pathology at old age, in an APOE4-dependent manner. GABA and glutamate may represent promising biomarkers and potential targets for early therapeutic intervention and prevention.
Gray matter-specific metabolic imaging with high-resolution atlas-based MRSI at 7 Tesla.Higher GABA and glutamate relate to ß-amyloid burden, in an APOE4-dependent manner.Gray matter GABA and glutamate identify older adults with high risk of future AD.GABA and glutamate might reflect altered synaptic and neuronal activity at early AD.
γ-羟基丁酸（GABA）和谷氨酸是对认知加工至关重要的神经递质。在此，我们研究了阿尔茨海默病（AD）临床表现出现之前GABA、谷氨酸与脑β-淀粉样蛋白（Aβ）负荷之间的关系。30名认知健康的成年人（年龄69.9±6岁）在7特斯拉的超高磁场强度下接受了基于高分辨率图谱的氢磁共振波谱成像（MRSI），以对灰质中的GABA和谷氨酸进行特异性评估。我们用正电子发射断层扫描评估了Aβ负荷以及AD的风险因素。较高的灰质GABA和谷氨酸与较高的Aβ负荷相关（=0.60，<0.05；=0.64，<0.02），载脂蛋白E-ε4等位基因（APOE4）对其有正向效应修饰作用（=0.01 - 0.03）。GABA和谷氨酸与言语情景记忆表现的纵向变化呈负相关（=-0.48；=0.02；=-0.50；=0.01）。GABA和谷氨酸的体内测量以APOE4依赖的方式反映了老年时的早期AD病理。GABA和谷氨酸可能是有前景的生物标志物以及早期治疗干预和预防的潜在靶点。
在7特斯拉下基于高分辨率图谱的MRSI进行灰质特异性代谢成像。较高的GABA和谷氨酸与β-淀粉样蛋白负荷相关，呈APOE4依赖的方式。灰质中的GABA和谷氨酸可识别未来患AD风险高的老年人。GABA和谷氨酸可能反映了早期AD时突触和神经元活动的改变。
