Simon J Schreiner, Jiri M G Van Bergen, Anton F Gietl, Alfred Buck, Christoph Hock, Klaas P Pruessmann, Anke Henning, Paul G Unschuld
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Higher gray matter GABA and glutamate related to higher Aß-burden (<i>ß </i>= 0.60, <i>p</i> < 0.05; <i>ß </i>= 0.64, <i>p</i> < 0.02), with positive effect modification by apolipoprotein-E-epsilon-4-allele (APOE4) (<i>p</i> = 0.01-0.03). GABA and glutamate negatively related to longitudinal change in verbal episodic memory performance (<i>ß </i>= -0.48; <i>p</i> = 0.02; <i>ß </i>= -0.50; <i>p</i> = 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.</p><p><strong>Highlights: </strong>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.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"16 2","pages":"e12587"},"PeriodicalIF":4.0000,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11058481/pdf/","citationCount":"0","resultStr":"{\"title\":\"Gray matter gamma-hydroxy-butyric acid and glutamate reflect beta-amyloid burden at old age.\",\"authors\":\"Simon J Schreiner, Jiri M G Van Bergen, Anton F Gietl, Alfred Buck, Christoph Hock, Klaas P Pruessmann, Anke Henning, Paul G Unschuld\",\"doi\":\"10.1002/dad2.12587\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <sup>1</sup>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 (<i>ß </i>= 0.60, <i>p</i> < 0.05; <i>ß </i>= 0.64, <i>p</i> < 0.02), with positive effect modification by apolipoprotein-E-epsilon-4-allele (APOE4) (<i>p</i> = 0.01-0.03). GABA and glutamate negatively related to longitudinal change in verbal episodic memory performance (<i>ß </i>= -0.48; <i>p</i> = 0.02; <i>ß </i>= -0.50; <i>p</i> = 0.01). 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引用次数: 0
摘要
γ-羟丁酸（GABA）和谷氨酸是对认知过程至关重要的神经递质。在此，我们研究了 GABA、谷氨酸和阿尔茨海默病（AD）临床表现前大脑ß-淀粉样蛋白（Aß）负荷之间的关系。30名认知健康的成年人（69.9 ± 6岁）在7特斯拉的超高磁场强度下接受了基于图谱的高分辨率1H-磁共振波谱成像（MRSI），以评估灰质中GABA和谷氨酸的特异性。我们通过正电子发射断层扫描评估了Aß负荷和AD的风险因素。灰质 GABA 和谷氨酸较高与 Aß 负担较高相关（ß = 0.60，p ß = 0.64，p p = 0.01-0.03）。GABA和谷氨酸与言语外显记忆表现的纵向变化呈负相关（ß = -0.48; p = 0.02; ß = -0.50; p = 0.01）。体内GABA和谷氨酸的测量结果以APOE4依赖性的方式反映了老年性痴呆的早期病理变化。GABA和谷氨酸可能是有希望的生物标志物，也是早期治疗干预和预防的潜在目标：灰质GABA和谷氨酸与ß-淀粉样蛋白负荷有关，且呈APOE4依赖性。灰质GABA和谷氨酸可识别未来AD高风险的老年人，GABA和谷氨酸可能反映AD早期突触和神经元活动的改变。
Gray matter gamma-hydroxy-butyric acid and glutamate reflect beta-amyloid burden at old age.
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 1H-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 (ß = 0.60, p < 0.05; ß = 0.64, p < 0.02), with positive effect modification by apolipoprotein-E-epsilon-4-allele (APOE4) (p = 0.01-0.03). GABA and glutamate negatively related to longitudinal change in verbal episodic memory performance (ß = -0.48; p = 0.02; ß = -0.50; p = 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.
Highlights: 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.
期刊介绍：
Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.
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