Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by 11C-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining 11C-Pittsburgh Compound B and 18F-FDG
Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by 11C-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining 11C-Pittsburgh Compound B and 18F-FDG
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DOI：
10.2967/jnumed.110.087031
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发表时间：
2012-01-01
影响因子：
9.3
通讯作者：
Nordberg, Agneta
中科院分区：
文献类型：
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作者：
Carter, Stephen F.;Scholl, Michael;Nordberg, Agneta
在死后阿尔茨海默病(AD)的脑组织中，星形胶质细胞与纤维淀粉样β蛋白(Aβ)斑块共存。因此，开发一种在活体内可视化星形胶质细胞的PET示踪剂，从而能够研究星形胶质细胞和纤维Aβ的区域分布是非常有意义的。对轻度认知障碍、轻度阿尔茨海默病患者和健康对照组进行了多示踪正电子发射计算机断层扫描，用C-11-氚-L-去甲肾上腺素(C-11-DED)法检测星形胶质细胞中单胺氧化酶B的表达。除了C-11-DED PET，还从患者那里获得了C-11-匹兹堡化合物B(C-11-PIB；纤维Aβ沉积)、F-18-FDG(葡萄糖代谢)、T1磁共振、脑脊液和神经心理学数据。方法：对8例MCI患者(平均年龄6 SD，62.6±-7.5岁，平均27.5±2.1岁)、7例AD患者(n=7，平均年龄65.1±6.3岁，平均24.4±/-5.7岁)和14例健康对照(n=14，平均年龄64.7±3.6岁)进行C-11-DED PET检查。采用改进的Patlak参考模型，以小脑灰质为参考，对C-11-DED数据进行动力学分析。使用数字脑图谱分析20-60分钟的C-11-DED数据。以小脑灰质为参照，计算每个患者的平均区域F-18-FDG摄取量和C-11-PIB滞留量。结果：对局部C-11-DED结合数据的方差分析显示，MCI患者双侧额叶和双侧顶叶皮质存在显著的群体效应，与结合增加有关。除3例MCI外，所有患者均显示高C-11-PIB滞留。MCI C-11-PIB阳性患者与对照组、MCI C-11-PIB(阴性)患者和AD患者相比，大部分皮质和皮质下C-11-DED结合增加。3种PET示踪剂之间没有发现地区性相关性。结论：MCI C-11-PIB+患者脑内C-11-DED结合增加，提示星形细胞增多症是AD发病的早期现象。
Astrocytes colocalize with fibrillar amyloid-beta (A beta) plaques in postmortem Alzheimer disease (AD) brain tissue. It is therefore of great interest to develop a PET tracer for visualizing astrocytes in vivo, enabling the study of the regional distribution of both astrocytes and fibrillar A beta. A multitracer PET investigation was conducted for patients with mild cognitive impairment (MCI), patients with mild AD, and healthy controls using C-11-deuterium-L-deprenyl (C-11-DED) to measure monoamine oxidase B located in astrocytes. Along with C-11-DED PET, C-11-Pittsburgh compound B (C-11-PIB; fibrillar A beta deposition), F-18-FDG (glucose metabolism), T1 MRI, cerebrospinal fluid, and neuropsychologic data were acquired from the patients. Methods: C-11-DED PET was performed in MCI patients (n = 8; mean age 6 SD, 62.6 +/- 7.5 y; mean Mini Mental State Examination, 27.5 +/- 2.1), AD patients (n = 7; mean age, 65.1 +/- 6.3 y; mean Mini Mental State Examination, 24.4 +/- 5.7), and healthy age-matched controls (n = 14; mean age, 64.7 +/- 3.6 y). A modified reference Patlak model, with cerebellar gray matter as a reference, was chosen for kinetic analysis of the C-11-DED data. C-11-DED data from 20 to 60 min were analyzed using a digital brain atlas. Mean regional F-18-FDG uptake and C-11-PIB retention were calculated for each patient, with cerebellar gray matter as a reference. Results: ANOVA analysis of the regional C-11-DED binding data revealed a significant group effect in the bilateral frontal and bilateral parietal cortices related to increased binding in the MCI patients. All patients, except 3 with MCI, showed high C-11-PIB retention. Increased C-11-DED binding in most cortical and subcortical regions was observed in MCI C-11-PIB+ patients relative to controls, MCI C-11-PIB (negative) patients, and AD patients. No regional correlations were found between the 3 PET tracers. Conclusion: Increased C-11-DED binding throughout the brain of the MCI C-11-PIB+ patients potentially suggests that astrocytosis is an early phenomenon in AD development.