PET amyloid ligand [11C]PIB uptake shows predominantly striatal increase in variant Alzheimer's disease
PET amyloid ligand [11C]PIB uptake shows predominantly striatal increase in variant Alzheimer's disease
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DOI：
10.1093/brain/awn107
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发表时间：
2008-07-01
期刊：
影响因子：
14.5
通讯作者：
Rinne, J. O.
中科院分区：
文献类型：
--
作者：
Koivunen, J.;Verkkoniemi, A.;Rinne, J. O.
伴有痉挛性轻瘫和早老性痴呆的变异型阿尔茨海默病（VarAD）与早老素1（PS-1）基因的某些突变相关，特别是导致外显子9（PS-1 E9）缺失的突变。VarAD在神经病理学上的特征在于存在异常大的A42阳性的无芯棉絮斑块（CWP），也没有营养不良的神经突。本研究的目的是确定[C-11]PIB是否会显示摄取增加，并作为VarAD中淀粉样蛋白蓄积的体内生物标志物。另一个目的是评估[C-11]PIB与另一组死亡VarAD患者大脑中A沉积物的量和类型的对应性。我们使用[C-11]PIB作为示踪剂，用PET研究了4例VarAD患者和8例健康对照。通过计算6090 min内每个体素的区域-小脑和区域-脑桥比率计算参数图像。采用自动感兴趣区域（ROI）分析分析[C-11]PIB摄取的组间差异。将[C-11]PIB摄取与另一组4名死亡VarAD患者脑中化学证实的A沉积进行比较。VarAD患者在纹状体（尾状核和壳核）、前扣带回和后扣带回、枕叶皮质和丘脑中的[C-11] PIB摄取显著高于对照组。在尾状核和壳核[C-11]中，PIB摄取（表示为区域-小脑比率）平均比对照组的平均值高43。扣带回前部（28个）和后部（27个）、枕叶皮质（21个）和丘脑（14个）的增加较小。所有VarAD患者均表现出类似的[C-11]PIB摄取增加的地形图模式。当以区域-脑桥比率表示摄取时，结果基本相似。[C-11]PIB成像显示VarAD患者的摄取增加，尤其是纹状体，可用于检测这些患者体内的淀粉样蛋白蓄积。[C-11]PIB摄取增加的模式与散发性阿尔茨海默病中描述的模式不同，并且类似于在具有某些早老素-1突变或淀粉样前体蛋白基因复制的阿尔茨海默病患者中观察到的模式，显示[C-11]PIB摄取主要在纹状体增加。
Variant Alzheimers disease (VarAD) with spastic paraparesis and presenile dementia is associated with certain mutations of the presenilin 1 (PS-1) gene, particularly those leading to deletion of exon 9 (PS-1 E9). VarAD is neuropathologically characterized by the presence of unusually large, A42 positive, non-cored cotton wool plaques (CWPs), also devoid of dystrophic neurites. The aim of the present study was to find out whether [C-11]PIB would show increased uptake and serve as an in vivo biomarker of amyloid accumulation in VarAD. A further aim was to assess the correspondence of the [C-11]PIB binding to the amount and type of A deposits in another group of deceased VarAD patients brains. We studied four patients with VarAD and eight healthy controls with PET using [C-11]PIB as tracer. Parametric images were computed by calculating the region-to-cerebellum and region-to-pons ratio in each voxel over 6090 min. Group differences in [C-11]PIB uptake were analysed with automated region-of-interest (ROI) analysis. [C-11]PIB uptake was compared to the immunohistochemically demonstrated deposition of A in the brains of another group of four deceased VarAD patients. Patients with VarAD had significantly higher [C-11] PIB uptake than the control group in the striatum (caudate nucleus and putamen), anterior and posterior cingulate gyrus, occipital cortex and thalamus. In the caudate and putamen [C-11]PIB uptake, expressed as region-to-cerebellum ratio, was on the average 43 greater than the mean of the control group. The increases in the anterior (28) and posterior (27) cingulate gyrus, occipital cortex (21) and thalamus (14) were smaller. All VarAD patients showed this similar topographical pattern of increased [C-11]PIB uptake. The results were essentially similar when the uptake was expressed as region-to-pons ratios. [C-11]PIB imaging shows increased uptake in patients with VarAD especially in the striatum, and it can be used to detect amyloid accumulation in vivo in these patients. The pattern of increased [C-11]PIB uptake is different from that described in sporadic Alzheimers disease and resembles that seen in Alzheimers disease patients with certain presenilin-1 mutations or amyloid precursor protein gene duplication showing predominantly striatal increase in [C-11]PIB uptake.