Early AD pathology in a [C-11]PiB-negative case: a PiB-amyloid imaging, biochemical, and immunohistochemical study.
Early AD pathology in a [C-11]PiB-negative case: a PiB-amyloid imaging, biochemical, and immunohistochemical study.
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DOI：
10.1007/s00401-012-0943-2
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发表时间：
2012-03
影响因子：
12.7
通讯作者：
Klunk WE
中科院分区：
文献类型：
--
作者：
Ikonomovic MD;Abrahamson EE;Price JC;Hamilton RL;Mathis CA;Paljug WR;Debnath ML;Cohen AD;Mizukami K;DeKosky ST;Lopez OL;Klunk WE
使用正电子发射断层扫描（PET）和[C-11]标记的匹兹堡化合物B（[C-11] Pi B）可在体内检测到脑中的β淀粉样蛋白（Aβ）沉积;然而，该技术的灵敏度尚未得到充分了解。在这项研究中，我们检查了一名临床诊断为可能的路易体痴呆和可能的阿尔茨海默病（AD），但在死亡前17个月成像时没有检测到[C-11]PiB PET滞留（[C-11]PiB（−））的个体的Aβ病理学。脑样本与区域匹配样本平行处理，样本来自临床诊断为可能AD且在死亡前10个月成像时[C-11]PiB PET扫描呈阳性（[C-11]PiB（+））的个体。在[C-11]PiB（-）的情况下，Aβ斑块稀疏，占据不到2%的皮质面积，并且被6-CN-PiB（PiB的高荧光衍生物）弱标记。相比之下，在[C-11]PiB（+）病例中，Aβ斑块占据高达12%的皮质面积，并被6-CN-PIB强烈标记。[C-11]PiB（-）病例的[H-3]PiB结合水平（<100 pmol/g）和Aβ1-42浓度（<500 pmol/g）较低，但额叶皮质中的Aβ1-42值（788 pmol/g）接近[C-11]PiB（+）病例中的皮质值（800- 1，700 pmol/g）。在[C-11]PiB（−）病例的几个皮质区域中，Aβ1-40水平在[C-11]PiB（+）病例皮质Aβ1-40值范围内。在[C-11]PiB（+）病例中，死前[C-11]PiB DVR值与Aβ1-42和Aβ1-40的区域匹配死后测量值相关性良好，仅在[C-11]PiB（-）病例中与Aβ1-42相关。在[C-11]PiB（−）病例中，[H-3]PiB结合水平与Aβ浓度的比值以及6-CN-PiB与Aβ斑块负荷的比值较低，表明大脑中的Aβ病理可能与[C-11]PiB滞留水平较低或检测不到相关。需要对更多[C-11]PiB PET尸检病例进行研究，以确定产生阳性[C-11]PiB PET信号所需的Aβ浓度和[H-3]PiB结合水平。
Amyloid-β (Aβ) deposits are detectable in the brain in vivo using positron emission tomography (PET) and [C-11]-labeled Pittsburgh Compound B ([C-11]PiB); however, the sensitivity of this technique is not well understood. In this study, we examined Aβ pathology in an individual who had clinical diagnoses of probable dementia with Lewy bodies and possible Alzheimer’s disease (AD) but with no detectable [C-11]PiB PET retention ([C-11]PiB(−)) when imaged 17 months prior to death. Brain samples were processed in parallel with region-matched samples from an individual with a clinical diagnosis of probable AD and a positive [C-11]PiB PET scan ([C-11]PiB(+)) when imaged 10 months prior to death. In the [C-11]PiB(−) case, Aβ plaques were sparse, occupying less than 2% cortical area, and were weakly labeled with 6-CN-PiB, a highly fluorescent derivative of PiB. In contrast, Aβ plaques occupied up to 12% cortical area in the [C-11]PiB(+) case, and were intensely labeled with 6-CN-PIB. The [C-11]PiB(−) case had low levels of [H-3]PiB binding (<100 pmol/g) and Aβ1–42 (<500 pmol/g) concentration except in the frontal cortex where Aβ1–42 values (788 pmol/g) approached cortical values in the [C-11]PiB(+) case (800–1,700 pmol/g). In several cortical regions of the [C-11]PiB(−) case, Aβ1–40 levels were within the range of cortical Aβ1–40 values in the [C-11]PiB(+) case. Antemortem [C-11]PiB DVR values correlated well with region-matched postmortem measures of Aβ1–42 and Aβ1–40 in the [C-11]PiB(+), and with Aβ1–42 only in the [C-11]PiB(−) case. The low ratios of [H-3]PiB binding levels to Aβ concentrations and 6-CN-PiB to Aβ plaque loads in the [C-11]PiB(−) case indicate that Aβ pathology in the brain may be associated with low or undetectable levels of [C-11]PiB retention. Studies in greater numbers of [C-11]PiB PET autopsy cases are needed to define the Aβ concentration and [H-3]PiB binding levels required to produce a positive [C-11]PiB PET signal.
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影响因子：
--
作者：
Haroutunian, V;Perl, DP;Mohs, RC
通讯作者：
Mohs, RC
DOI：
10.1006/bbrc.2000.3490
发表时间：
2000-09-24
影响因子：
3.1
作者：
Harigaya, Y;Saido, TC;Younkin, SG
通讯作者：
Younkin, SG
影响因子：
6.1
作者：
Klunk, WE;Wang, YM;Mathis, CA
通讯作者：
Mathis, CA
影响因子：
--
作者：
Aizenstein, Howard Jay;Nebes, Robert D.;Saxton, Judith A.;Price, Julie C.;Mathis, Chester A.;Tsopelas, Nicholas D.;Ziolko, Scott K.;James, Jeffrey A.;Snitz, Beth E.;Houck, Patricia R.;Bi, Wenzhu;Cohen, Ann D.;Lopresti, Brian J.;DeKosky, Steven T.;Halligan, Edythe M.;Klunk, William E.
通讯作者：
Klunk, William E.
影响因子：
11.2
作者：
Klunk, WE;Engler, H;Långström, B
通讯作者：
Långström, B