Institute for Regenerative Medicine (IREM), University of Zurich, Schlieren, Switzerland.
Department of Nuclear Medicine, University Hospital of Zurich, Zurich, Switzerland.
Brain Behav. 2020 Jun;10(6):e01632. doi: 10.1002/brb3.1632. Epub 2020 Apr 18.
Metabotropic glutamate receptors play a critical role in the pathogenesis of Alzheimer's disease due to their involvement in processes of memory formation, neuroplasticity, and synaptotoxity. The objective of the current study was to study mGluR5 availability measured by [ C]-ABP688 (ABP) in patients with clinically diagnosed Alzheimer's dementia (AD).
A bolus-infusion protocol of [ C]-ABP688 was applied in 9 subjects with AD and 10 cognitively healthy controls (Controls) to derive distribution volume estimates of mGluR5. Furthermore, we also estimated cerebral perfusion by averaging early frame signal of initial ABP bolus injection.
Subjects with Alzheimer's dementia (mean age: 77.3/SD 5.7) were older than controls (mean age: 68.5/SD: 9.6) and scored lower on the MMSE (22.1/SD2.7 vs. 29.0/SD0.8). There were no overall differences in ABP signal. However, distribution volume ratio (DVR) for ABP was reduced in the bilateral hippocampus (AD: 1.34/SD: 0.40 vs. Control: 1.84/SD:0.31, p = .007) and the bilateral amygdala (AD:1.86/SD:0.26 vs. Control:2.33/SD:0.37 p = .006) in AD patients compared to controls. Estimate of cerebral blood flow was reduced in the bilateral hippocampus in AD (AD:0.75/SD:0.10 vs. Control:0.86/SD:0.09 p = .02).
Our findings demonstrate reduced mGluR5 binding in the hippocampus and amygdala in Alzheimer's dementia. Whether this is due to synaptic loss and/or consecutive reduction of potential binding sites or reflects disease inherent mechanisms remains to be elucidated in future studies.
代谢型谷氨酸受体在阿尔茨海默病的发病机制中起着关键作用，因为它们参与了记忆形成、神经可塑性和突触毒性等过程。本研究的目的是研究通过 [C]-ABP688（ABP）测量的在临床上被诊断为阿尔茨海默病痴呆（AD）的患者的 mGluR5 可利用性。
在 9 名 AD 患者和 10 名认知健康对照者（对照组）中应用 [C]-ABP688 脉冲输注方案，得出 mGluR5 的分布容积估计值。此外，我们还通过平均初始 ABP 脉冲注射的早期帧信号来估计脑灌注。
AD 患者（平均年龄：77.3/SD 5.7）比对照组（平均年龄：68.5/SD：9.6）年龄大，且 MMSE 评分较低（22.1/SD2.7 比 29.0/SD0.8）。ABP 信号没有总体差异。然而，双侧海马（AD：1.34/SD：0.40 比对照组：1.84/SD：0.31，p=0.007）和双侧杏仁核（AD：1.86/SD：0.26 比对照组：2.33/SD：0.37，p=0.006）的 ABP 分布容积比在 AD 患者中降低。AD 患者双侧海马的脑血流估计值降低（AD：0.75/SD：0.10 比对照组：0.86/SD：0.09，p=0.02）。
我们的发现表明，在阿尔茨海默病患者的海马体和杏仁核中，mGluR5 结合减少。这种情况是由于突触丢失和/或潜在结合位点的连续减少，还是反映了疾病固有的机制，尚待进一步研究阐明。
