Frontotemporal lobar degeneration proteinopathies have disparate microscopic patterns of white and grey matter pathology.
Frontotemporal lobar degeneration proteinopathies have disparate microscopic patterns of white and grey matter pathology.
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DOI：
10.1186/s40478-021-01129-2
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发表时间：
2021-02-23
影响因子：
7.1
通讯作者：
Irwin DJ
中科院分区：
文献类型：
--
作者：
Giannini LAA;Peterson C;Ohm D;Xie SX;McMillan CT;Raskovsky K;Massimo L;Suh E;Van Deerlin VM;Wolk DA;Trojanowski JQ;Lee EB;Grossman M;Irwin DJ
具有tau包涵体（FTLD-Tau）或TDP-43包涵体（FTLD-TDP）的额颞叶变性蛋白病与临床相似的表型相关。然而，这些不同的蛋白质病可能在白色物质（WM）和相邻灰质（GM）中的细胞严重程度和区域分布方面存在差异，这一点尚未得到充分研究。我们使用经验证的数字图像方法在大型尸检队列（n = 92; FTLD-Tau = 37，FTLD-TDP = 55）中对皮质下WM和相邻GM进行了神经病理学研究。23例FTLD-Tau患者和42例FTLD-TDP患者的生前临床表型为行为变异性额颞叶痴呆（bvFTD），14例FTLD-Tau患者和13例FTLD-TDP患者的生前临床表型为原发性进行性失语（PPA）。我们使用线性混合效应模型：（1）比较蛋白质病之间的WM病理负荷;（2）使用勒克索坚牢蓝（LFB）髓鞘染色研究WM病理负荷与WM变性之间的关系;（3）研究临床病理组中病理负荷的区域模式。与FTLD-TDP相比，FTLD-Tau的WM病理负荷在各区域更大（β = 4.21，SE = 0.34，p < 0.001），并且与FTLD-Tau（β = 0.32，SE = 0.10，p = 0.002）和FTLD-TDP（β = 0.40，SE = 0.08，p < 0.001）的WM变性程度相关。FTLD-Tau的WM变性比FTLD-TDP更大，特别是在中额和前扣带回区域（p < 0.05）。WM和GM包涵体的不同区域模式表征了FTLD-Tau和FTLD-TDP蛋白病，并部分与临床表型相关。在FTLD-Tau中，WM病理在非流畅变异PPA的背外侧额叶皮层中特别严重，GM病理在背外侧和边缘额叶区域中具有一些变化。显然，FTLD-TDP的WM区域变异性很小，但在bvFTD和PPA的腹内侧前额叶区域显示出重度GM病理负荷。综上所述，FTLD-Tau和FTLD-TDP蛋白病具有不同的WM和GM病理严重程度和区域分布，这可能影响其临床表现，总体上WM病理严重程度更高是Tau病的显著特征。
Frontotemporal lobar degeneration proteinopathies with tau inclusions (FTLD-Tau) or TDP-43 inclusions (FTLD-TDP) are associated with clinically similar phenotypes. However, these disparate proteinopathies likely differ in cellular severity and regional distribution of inclusions in white matter (WM) and adjacent grey matter (GM), which have been understudied. We performed a neuropathological study of subcortical WM and adjacent GM in a large autopsy cohort (n = 92; FTLD-Tau = 37, FTLD-TDP = 55) using a validated digital image approach. The antemortem clinical phenotype was behavioral-variant frontotemporal dementia (bvFTD) in 23 patients with FTLD-Tau and 42 with FTLD-TDP, and primary progressive aphasia (PPA) in 14 patients with FTLD-Tau and 13 with FTLD-TDP. We used linear mixed-effects models to: (1) compare WM pathology burden between proteinopathies; (2) investigate the relationship between WM pathology burden and WM degeneration using luxol fast blue (LFB) myelin staining; (3) study regional patterns of pathology burden in clinico-pathological groups. WM pathology burden was greater in FTLD-Tau compared to FTLD-TDP across regions (beta = 4.21, SE = 0.34, p < 0.001), and correlated with the degree of WM degeneration in both FTLD-Tau (beta = 0.32, SE = 0.10, p = 0.002) and FTLD-TDP (beta = 0.40, SE = 0.08, p < 0.001). WM degeneration was greater in FTLD-Tau than FTLD-TDP particularly in middle-frontal and anterior cingulate regions (p < 0.05). Distinct regional patterns of WM and GM inclusions characterized FTLD-Tau and FTLD-TDP proteinopathies, and associated in part with clinical phenotype. In FTLD-Tau, WM pathology was particularly severe in the dorsolateral frontal cortex in nonfluent-variant PPA, and GM pathology in dorsolateral and paralimbic frontal regions with some variation across tauopathies. Differently, FTLD-TDP had little WM regional variability, but showed severe GM pathology burden in ventromedial prefrontal regions in both bvFTD and PPA. To conclude, FTLD-Tau and FTLD-TDP proteinopathies have distinct severity and regional distribution of WM and GM pathology, which may impact their clinical presentation, with overall greater severity of WM pathology as a distinguishing feature of tauopathies.
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影响因子：
7.1
作者：
Fatima M;Tan R;Halliday GM;Kril JJ
通讯作者：
Kril JJ
DOI：
10.1007/s12031-011-9589-0
发表时间：
2011-11
期刊：
Journal of molecular neuroscience : MN
影响因子：
--
作者：
Dickson DW;Kouri N;Murray ME;Josephs KA
通讯作者：
Josephs KA
影响因子：
4.3
作者：
Giannini, Lucia A. A.;Xie, Sharon X.;Irwin, David J.
通讯作者：
Irwin, David J.
影响因子：
3.2
作者：
Irwin, David J.;Byrne, Matthew D.;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
38.1
作者：
Grossman, Murray
通讯作者：
Grossman, Murray