PDF(Pubmed)
Abstract：
Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the initial pathophysiological mechanism of Alzheimer\'s disease (AD). The study aims to investigate the association between mGluR5 availability and AD\'s biomarkers and cognitive function.
We examined 35 individuals with mGluR5 tracer [18F]PSS232 to assess mGluR5 availability, and with [18F]Florbetapir PET to assess global amyloid deposition, and [18F]FDG PET to assess glucose metabolism. The plasma neurofilament light (NfL) and p-tau181 levels in a subset of individuals were measured (n = 27). The difference in mGluR5 availability between the AD and normal control (NC) groups was explored. The associations of mGluR5 availability with amyloid deposition, glucose metabolism, gray matter volume (GMV), neuropsychological assessment scores, and plasma biomarkers were analyzed.
The mGluR5 availability was significantly reduced in AD patients\' hippocampus and parahippocampal gyrus compared to NCs. Global amyloid deposition was positively associated with mGluR5 availability in the AD group and reversely associated in the NC group. The mGluR5 availability was positively correlated with regional glucose metabolism in the overall and stratified analyses. The availability of mGluR5 in the hippocampus and parahippocampal gyrus demonstrated a strong relationship with the GMV of the medial temporal lobe, plasma p-tau181 or NfL levels, and global cognitive performance.
[18F]PSS232 PET can quantify the changes of mGluR5 availability in the progression of AD. mGluR5 availability correlated not only with neuropathological biomarkers of AD but also with neurodegenerative biomarkers and cognitive performance. mGluR5 may be a novel neurodegenerative biomarker, and whether mGluR5 could be a potential therapeutic target for AD needs to be further studied.
We examined 35 individuals with mGluR5 tracer [18F]PSS232 to assess mGluR5 availability, and with [18F]Florbetapir PET to assess global amyloid deposition, and [18F]FDG PET to assess glucose metabolism. The plasma neurofilament light (NfL) and p-tau181 levels in a subset of individuals were measured (n = 27). The difference in mGluR5 availability between the AD and normal control (NC) groups was explored. The associations of mGluR5 availability with amyloid deposition, glucose metabolism, gray matter volume (GMV), neuropsychological assessment scores, and plasma biomarkers were analyzed.
The mGluR5 availability was significantly reduced in AD patients\' hippocampus and parahippocampal gyrus compared to NCs. Global amyloid deposition was positively associated with mGluR5 availability in the AD group and reversely associated in the NC group. The mGluR5 availability was positively correlated with regional glucose metabolism in the overall and stratified analyses. The availability of mGluR5 in the hippocampus and parahippocampal gyrus demonstrated a strong relationship with the GMV of the medial temporal lobe, plasma p-tau181 or NfL levels, and global cognitive performance.
[18F]PSS232 PET can quantify the changes of mGluR5 availability in the progression of AD. mGluR5 availability correlated not only with neuropathological biomarkers of AD but also with neurodegenerative biomarkers and cognitive performance. mGluR5 may be a novel neurodegenerative biomarker, and whether mGluR5 could be a potential therapeutic target for AD needs to be further studied.
摘要：
背景：代谢型谷氨酸受体5（mGluR5）参与调节整合脑功能和突触传递。异常的mGluR5信号传导和相关的突触衰竭在阿尔茨海默病(AD)的最初病理生理机制中起着关键作用。该研究旨在探讨mGluR5的可用性与AD的生物标志物和认知功能之间的关系。
方法：我们用mGluR5示踪剂[18F]PSS232检查了35名个体，以评估mGluR5的可用性。并用[18F]FlorbetapirPET评估整体淀粉样蛋白沉积，和[18F]FDGPET评估葡萄糖代谢。测量了一部分个体中的血浆神经丝光（NfL）和p-tau181水平（n=27）。研究了AD组和正常对照(NC)组之间的mGluR5可用性的差异。mGluR5可用性与淀粉样蛋白沉积的关联，葡萄糖代谢，灰质体积（GMV），神经心理学评估分数，和血浆生物标志物进行了分析。
结果：与NC相比，AD患者海马和海马旁回的mGluR5利用率显著降低。在AD组中，整体淀粉样蛋白沉积与mGluR5的可用性呈正相关，而在NC组中呈相反相关。在总体和分层分析中，mGluR5的可用性与区域葡萄糖代谢呈正相关。海马和海马旁回中mGluR5的可用性与内侧颞叶的GMV密切相关，血浆p-tau181或NfL水平，和全球认知表现。
结论：[18F]PSS232PET可以量化mGluR5可用性在AD进展中的变化。mGluR5的可用性不仅与AD的神经病理学生物标志物相关，而且与神经退行性生物标志物和认知表现相关。mGluR5可能是一种新型的神经退行性生物标志物，mGluR5是否可能成为AD的潜在治疗靶点还有待进一步研究。
方法：我们用mGluR5示踪剂[18F]PSS232检查了35名个体，以评估mGluR5的可用性。并用[18F]FlorbetapirPET评估整体淀粉样蛋白沉积，和[18F]FDGPET评估葡萄糖代谢。测量了一部分个体中的血浆神经丝光（NfL）和p-tau181水平（n=27）。研究了AD组和正常对照(NC)组之间的mGluR5可用性的差异。mGluR5可用性与淀粉样蛋白沉积的关联，葡萄糖代谢，灰质体积（GMV），神经心理学评估分数，和血浆生物标志物进行了分析。
结果：与NC相比，AD患者海马和海马旁回的mGluR5利用率显著降低。在AD组中，整体淀粉样蛋白沉积与mGluR5的可用性呈正相关，而在NC组中呈相反相关。在总体和分层分析中，mGluR5的可用性与区域葡萄糖代谢呈正相关。海马和海马旁回中mGluR5的可用性与内侧颞叶的GMV密切相关，血浆p-tau181或NfL水平，和全球认知表现。
结论：[18F]PSS232PET可以量化mGluR5可用性在AD进展中的变化。mGluR5的可用性不仅与AD的神经病理学生物标志物相关，而且与神经退行性生物标志物和认知表现相关。mGluR5可能是一种新型的神经退行性生物标志物，mGluR5是否可能成为AD的潜在治疗靶点还有待进一步研究。
