Yan Wang, Jie Wang, Xing Chen, Zengping Lin, Zhiwen You, Kun He, Tengfei Guo, Jun Zhao, Qi Huang, Ruiqing Ni, Yihui Guan, Binyin Li, Fang Xie
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The relationships among mGluR5 availability, tau deposition, and neuropsychological assessment were analyzed using Spearman's correlation and mediation analyses.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>CI patients had lower mGluR5 in the hippocampus than CU (standardized uptake value ratio [SUVr]: 2.03 ± 0.25 vs 1.79 ± 0.17, <i>p</i> = 0.003). Hippocampal mGluR5 was negatively associated with hippocampal tau deposition (<i>r</i> = −.46, <i>p</i> = 0.003) and positively associated with cognitive performance, but only in women. Hippocampal tau deposition mediated the effect of mGluR5 on cognitive performance.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>Reduced hippocampal mGluR5 is negatively related with tau deposition in most cortical regions and positively associated with cognitive performance, making it a promising biomarker for AD diagnosis and therapy.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Cognitively impaired (CI) patients exhibited lower metabotropic glutamate receptor 5 (mGluR5) availability in the hippocampus than cognitively unimpaired (CU) subjects.</li>\n \n <li>Hippocampal mGluR5 availability was negatively associated with tau deposition in widespread cortex.</li>\n \n <li>Hippocampal mGluR5 availability was positively associated with cognitive performance.</li>\n \n <li>The close association of mGluR5 with tau and cognition performance exists only in females.</li>\n \n <li>Tau pathology mediated the relationship between mGluR5 availability and cognition.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":11.1000,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70004","citationCount":"0","resultStr":"{\"title\":\"Tau pathology is associated with postsynaptic metabotropic glutamate receptor 5 (mGluR5) in early Alzheimer's disease in a sex-specific manner\",\"authors\":\"Yan Wang, Jie Wang, Xing Chen, Zengping Lin, Zhiwen You, Kun He, Tengfei Guo, Jun Zhao, Qi Huang, Ruiqing Ni, Yihui Guan, Binyin Li, Fang Xie\",\"doi\":\"10.1002/alz.70004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> INTRODUCTION</h3>\\n \\n <p>To investigate the associations of metabotropic glutamate receptor 5 (mGluR5) with tau deposition and cognitive ability in patients with early Alzheimer's disease (AD).</p>\\n </section>\\n \\n <section>\\n \\n <h3> METHODS</h3>\\n \\n <p>Twenty-six cognitively impaired (CI) and 14 cognitively unimpaired (CU) individuals underwent mGluR5 positron emission tomography (PET) ([<sup>18</sup>F]PSS232), amyloid PET ([<sup>18</sup>F]florbetapir), and tau PET ([<sup>18</sup>F]MK6240), and neuropsychological assessment. 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引用次数: 0
摘要
探讨代谢性谷氨酸受体5 （mGluR5）与早期阿尔茨海默病（AD）患者tau沉积和认知能力的关系。方法26例认知受损（CI）和14例认知未受损（CU）患者接受了mGluR5正电子发射断层扫描（PET） （[18F]PSS232）、淀粉样蛋白PET （[18F]florbetapir）和tau PET ([18F]MK6240)，并进行了神经心理学评估。采用Spearman相关分析和中介分析分析mGluR5可用性、tau沉积和神经心理评估之间的关系。结果CI患者海马mGluR5低于CU患者（标准化摄取值比[SUVr]: 2.03±0.25 vs 1.79±0.17,p = 0.003）。海马mGluR5与海马tau沉积呈负相关（r =−）。46, p = 0.003)，与认知表现呈正相关，但仅适用于女性。海马tau沉积介导mGluR5对认知表现的影响。海马mGluR5减少与大多数皮质区域的tau沉积呈负相关，与认知能力呈正相关，使其成为AD诊断和治疗的有希望的生物标志物。认知受损（CI）患者海马中代谢性谷氨酸受体5 （mGluR5）的可用性低于认知未受损（CU）受试者。海马mGluR5可用性与广泛皮层的tau沉积呈负相关。海马mGluR5可用性与认知表现呈正相关。mGluR5与tau蛋白和认知能力密切相关仅存在于女性中。Tau病理介导mGluR5可用性与认知之间的关系。
Tau pathology is associated with postsynaptic metabotropic glutamate receptor 5 (mGluR5) in early Alzheimer's disease in a sex-specific manner
INTRODUCTION
To investigate the associations of metabotropic glutamate receptor 5 (mGluR5) with tau deposition and cognitive ability in patients with early Alzheimer's disease (AD).
METHODS
Twenty-six cognitively impaired (CI) and 14 cognitively unimpaired (CU) individuals underwent mGluR5 positron emission tomography (PET) ([18F]PSS232), amyloid PET ([18F]florbetapir), and tau PET ([18F]MK6240), and neuropsychological assessment. The relationships among mGluR5 availability, tau deposition, and neuropsychological assessment were analyzed using Spearman's correlation and mediation analyses.
RESULTS
CI patients had lower mGluR5 in the hippocampus than CU (standardized uptake value ratio [SUVr]: 2.03 ± 0.25 vs 1.79 ± 0.17, p = 0.003). Hippocampal mGluR5 was negatively associated with hippocampal tau deposition (r = −.46, p = 0.003) and positively associated with cognitive performance, but only in women. Hippocampal tau deposition mediated the effect of mGluR5 on cognitive performance.
DISCUSSION
Reduced hippocampal mGluR5 is negatively related with tau deposition in most cortical regions and positively associated with cognitive performance, making it a promising biomarker for AD diagnosis and therapy.
Highlights
Cognitively impaired (CI) patients exhibited lower metabotropic glutamate receptor 5 (mGluR5) availability in the hippocampus than cognitively unimpaired (CU) subjects.
Hippocampal mGluR5 availability was negatively associated with tau deposition in widespread cortex.
Hippocampal mGluR5 availability was positively associated with cognitive performance.
The close association of mGluR5 with tau and cognition performance exists only in females.
Tau pathology mediated the relationship between mGluR5 availability and cognition.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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