Neuropathological heterogeneity in frontotemporal lobar degeneration with TDP-43 proteinopathy: a quantitative study of 94 cases using principal components analysis.
Neuropathological heterogeneity in frontotemporal lobar degeneration with TDP-43 proteinopathy: a quantitative study of 94 cases using principal components analysis.
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DOI：
10.1007/s00702-009-0350-6
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发表时间：
2010-02
影响因子：
3.3
通讯作者：
Cairns, Nigel J.
中科院分区：
文献类型：
--
作者：
Armstrong, Richard A.;Ellis, William;Hamilton, Ronald L.;Mackenzie, Ian R. A.;Hedreen, John;Gearing, Marla;Montine, Thomas;Vonsattel, Jean-Paul;Head, Elizabeth;Lieberman, Andrew P.;Cairns, Nigel J.
关键词：
研究表明，额颞叶变性伴43 kDa交互反应性dna结合蛋白（TDP-43）蛋白病（FTLD-TDP）具有异质性，可分为四或五种亚型。为了确定亚型的异质性程度和有效性，我们使用密度和主成分分析（PCA）的定量估计研究了94例FTLD-TDP患者额叶和颞叶内的神经病理变异。基于TDP-43免疫反应性神经元胞浆包涵体、少突胶质包涵体、神经元核内包涵体、营养不良神经突、存活神经元、增大神经元和空泡化密度的PCA表明，病例没有被划分为不同的亚型。液泡密度的变化是病例间差异的最大来源。单独基于TDP-43病理的PCA提示FTLD-TDP伴颗粒前蛋白（GRN）突变的病例有一定程度的分离。四种亚型的病理表型均有重叠，但亚型1和亚型4最显著。同时存在运动神经元疾病（MND）或海马硬化（HS）的病例也出现一定程度的分离。我们认为：(1)FTLD-TDP的病理变异最好被描述为一个没有明显不同亚型的“连续体”，(2)空泡化是变异的单一最大来源，反映了疾病的“阶段”，(3)在FTLD-TDP“连续体”中，GRN突变和共存的MND或HS可能有更独特的病理。
Studies suggest that frontotemporal lobar degeneration with transactive response DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP) is heterogeneous with division into four or five subtypes. To determine the degree of heterogeneity and the validity of the subtypes, we studied neuropathological variation within the frontal and temporal lobes of 94 cases of FTLD-TDP using quantitative estimates of density and principal components analysis (PCA). A PCA based on the density of TDP-43 immunoreactive neuronal cytoplasmic inclusions, oligodendroglial inclusions, neuronal intranuclear inclusions, and dystrophic neurites, surviving neurons, enlarged neurons, and vacuolation suggested that cases were not segregated into distinct subtypes. Variation in the density of the vacuoles was the greatest source of variation between cases. A PCA based on TDP-43 pathology alone suggested that cases of FTLD-TDP with progranulin (GRN) mutation segregated to some degree. The pathological phenotype of all four subtypes overlapped but subtypes 1 and 4 were the most distinctive. Cases with coexisting motor neuron disease (MND) or hippocampal sclerosis (HS) also appeared to segregate to some extent. We suggest: (1) pathological variation in FTLD-TDP is best described as a ‘continuum’ without clearly distinct subtypes, (2) vacuolation was the single greatest source of variation and reflects the ‘stage’ of the disease, and (3) within the FTLD-TDP ‘continuum’ cases with GRN mutation and with coexisting MND or HS may have a more distinctive pathology.
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影响因子：
64.8
作者：
Cruts, Marc;Gijselinck, Ilse;Van Broeckhoven, Christine
通讯作者：
Van Broeckhoven, Christine
影响因子：
6
作者：
Cairns, NJ;Zhukareva, V;Trojanowski, JQ
通讯作者：
Trojanowski, JQ
影响因子：
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作者：
Josephs, Keith A.;Whitwell, Jennifer L.;Dickson, Dennis W.
通讯作者：
Dickson, Dennis W.
影响因子：
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作者：
Cairns, Nigel J.;Neumann, Manuela;Mackenzie, Ian R. A.
通讯作者：
Mackenzie, Ian R. A.
影响因子：
9.9
作者：
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通讯作者：
Bigio, E. H.