Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County, Stockholm, Sweden.
Personalized Medicine, R&D, PET Science Centre, AstraZeneca, Stockholm, Sweden.
Synapse. 2022 Jun;76(7-8):e22235. doi: 10.1002/syn.22235. Epub 2022 May 28.
Decreased 5-HT receptor binding has been associated with Alzheimer's disease (AD) and interpreted as a consequence of neuron loss. The purpose of the present study was to compare [ C]WAY100635 binding to the 5-HT receptor in the hippocampus, entorhinal cortex, amygdala and pericalcarine cortex in mild AD patients and elderly controls. AD patients (n = 7) and elderly control subjects (n = 8) were examined with positron emission tomography (PET) and [ C]WAY100635. PET data acquisition was performed with an ECAT EXACT HR system. Wavelet-aided parametric images of nondisplaceable binding potential (BP ) were generated using Logan's graphical analysis with cerebellum as the reference region. Correction for partial volume effects was performed with the Müller-Gärtner method. Regions of interest (ROIs) were applied to the individual parametric images, and the regional BP was calculated as the average parametric voxel value within each ROI. In addition to comparisons between subject groups, correlations between BP values and scores on the Mini-Mental State Examination, Disability Assessment for Dementia (DAD), and Neuropsychiatric Inventory were expressed by Pearson correlation coefficients. Mean regional BP was lower in AD patients than in control subjects, and the difference was statistically significant for the hippocampus, entorhinal cortex, and amygdala. A statistically significant correlation was obtained between hippocampal BP values and DAD scores. The results of the present study corroborate and extend previous findings of decreased 5-HT binding in AD and strengthen the support for 5-HT receptor PET as a tool for the assessment of neurodegenerative changes in mild AD.
5-羟色胺(5-HT)受体结合减少与阿尔茨海默病(AD)有关,并被解释为神经元丢失的结果。本研究的目的是比较轻度 AD 患者和老年对照组海马、内嗅皮质、杏仁核和距状皮层中[C]WAY100635 与 5-HT 受体的结合。AD 患者(n=7)和老年对照组(n=8)接受正电子发射断层扫描(PET)和[C]WAY100635 检查。PET 数据采集使用 ECAT EXACT HR 系统进行。使用基于 Logan 图形分析的小波辅助无置换结合势(BP)参数图像,以小脑为参考区域。使用 Müller-Gärtner 方法进行部分容积效应校正。将感兴趣区(ROI)应用于个体参数图像,并将 ROI 内的每个参数体素的平均参数体素值计算为区域 BP。除了对受试者组之间进行比较外,还通过 Pearson 相关系数表示 BP 值与简易精神状态检查(MMSE)、痴呆残疾评估(DAD)和神经精神问卷评分之间的相关性。AD 患者的平均区域 BP 低于对照组,且在海马、内嗅皮质和杏仁核中差异具有统计学意义。还获得了海马 BP 值与 DAD 评分之间的统计学显著相关性。本研究结果证实并扩展了之前关于 AD 中 5-HT 结合减少的发现,并为 5-HT 受体 PET 作为评估轻度 AD 神经退行性变化的工具提供了更多支持。