[(18)F]AV-1451 binding in vivo mirrors the expected distribution of TDP-43 pathology in the semantic variant of primary progressive aphasia.
[(18)F]AV-1451 binding in vivo mirrors the expected distribution of TDP-43 pathology in the semantic variant of primary progressive aphasia.
复制标题
DOI：
10.1136/jnnp-2017-316402
复制
发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Rowe JB
中科院分区：
文献类型：
--
作者：
Bevan-Jones WR;Cope TE;Jones PS;Passamonti L;Hong YT;Fryer TD;Arnold R;Allinson KSJ;Coles JP;Aigbirhio FI;Patterson K;O'Brien JT;Rowe JB
语义性痴呆，包括原发性进行性失语症的语义变异(SvPPA)，与TAR-DNA结合蛋白43(TDP-43)C型病理密切相关。它提供了一个有用的模型，用来测试假定的tau配体[18F]AV-1451在体内结合的特异性，它在额颞叶退行性病变中升高。7名患者(5名svPPA患者和2名右侧语义性痴呆患者)和12名健康对照接受了使用[18F]AV-1451的正电子发射断层扫描脑成像。采用了两种独立的前处理方法。在这两种方法中，所有患者的颞叶结合势(BPND(不可移位结合势))都明显升高，根据他们的临床症状和原始图像明显偏侧。感兴趣区分析证实，BPND在颞区、脑岛和梭状回显著增加，这与已知的语义性痴呆影响最大的区域一致。基于[18F]AV-1451结合潜力分布的层次聚类分析，将语义性痴呆与对照区分开来，敏感度和特异度分别为86%和100%。[18F]AV-1451在体内结合了可能含有TDP-43的区域，而不是明显的tau病理。虽然这表明[18F]AV-1451是非tau靶点，但语义性痴呆的病理区域通常不包含最近提出的[18F]AV-1451的“脱靶”结合位点的显著水平，如神经元单胺氧化酶或神经黑色素。尸检和纵向数据将有助于评估[18F]AV-1451在区分和追踪不同类型的额颞叶变性方面的作用。
Semantic dementia, including the semantic variant of primary progressive aphasia (svPPA), is strongly associated with TAR-DNA binding protein 43 (TDP-43) type C pathology. It provides a useful model in which to test the specificity of in vivo binding of the putative tau ligand [18F]AV-1451, which is elevated in frontotemporal lobar degeneration tauopathies. Seven patients (five with svPPA and two with ‘right’ semantic dementia) and 12 healthy controls underwent positron emission tomography brain imaging with [18F]AV-1451. Two independent preprocessing methods were used. For both methods, all patients had clearly elevated binding potential (BPND (non-displaceable binding potential)) in temporal lobes, lateralising according to their clinical syndrome and evident in raw images. Region of interest analyses confirmed that BPND was significantly increased in temporal regions, insula and fusiform gyrus, consistent with those areas known to be most affected in semantic dementia. Hierarchical cluster analysis, based on the distribution of [18F]AV-1451 binding potential, separated semantic dementia from controls with 86% sensitivity and 100% specificity. [18F]AV-1451 binds in vivo regions that are likely to contain TDP-43 and not significant tau pathology. While this suggests a non-tau target for [18F]AV-1451, the pathological regions in semantic dementia do not normally contain significant levels of recently proposed ‘off target’ binding sites for [18F]AV-1451, such as neuronal monoamine oxidase or neuromelanin. Postmortem and longitudinal data will be useful to assess the utility of [18F]AV-1451 to differentiate and track different types of frontotemporal lobar degeneration.
登录
查看更多内容
影响因子：
7.1
作者：
Lowe VJ;Curran G;Fang P;Liesinger AM;Josephs KA;Parisi JE;Kantarci K;Boeve BF;Pandey MK;Bruinsma T;Knopman DS;Jones DT;Petrucelli L;Cook CN;Graff-Radford NR;Dickson DW;Petersen RC;Jack CR Jr;Murray ME
通讯作者：
Murray ME
影响因子：
2.9
作者：
Bevan-Jones, W. Richard;Surendranathan, Ajenthan;O'Brien, John T.
通讯作者：
O'Brien, John T.
影响因子：
14
作者：
Sander, Kerstin;Lashley, Tammaryn;Arstad, Erik
通讯作者：
Arstad, Erik
影响因子：
5.7
作者：
Genovese, CR;Lazar, NA;Nichols, T
通讯作者：
Nichols, T
影响因子：
14.5
作者：
Hansen, Allan K.;Knudsen, Karoline;Borghammer, Per
通讯作者：
Borghammer, Per