Astroglial tau pathology alone preferentially concentrates at sulcal depths in chronic traumatic encephalopathy neuropathologic change.
Astroglial tau pathology alone preferentially concentrates at sulcal depths in chronic traumatic encephalopathy neuropathologic change.
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DOI：
10.1093/braincomms/fcaa210
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发表时间：
2020
影响因子：
4.8
通讯作者：
Stewart W
中科院分区：
文献类型：
--
作者：
Arena JD;Johnson VE;Lee EB;Gibbons GS;Smith DH;Trojanowski JQ;Stewart W
目前的诊断标准的创伤性脑损伤相关的神经变性，慢性创伤性脑病的神经病理学评价，定义为过度磷酸化的tau蛋白免疫反应神经元和星形胶质细胞的分布在斑片状皮质，聚集在周围的小血管，并显示优先定位到脑沟的深度的病理特征性病变。然而，尽管采用诊断标准，还没有正式评估的皮质分布的特定细胞成分定义慢性创伤性脑病神经病理学变化。为了解决这个问题，我们进行了全面的映射过度磷酸化tau蛋白免疫反应神经元缠结和刺状星形胶质细胞有助于慢性创伤性脑病的神经病理变化。从格拉斯哥创伤性脑损伤档案和宾夕法尼亚大学神经退行性疾病研究中心脑库中，材料选自具有已知慢性创伤性脑病神经病理学改变的患者，或者在暴露于重复的轻度脑损伤之后，或者在暴露于（运动员n = 17;非运动员n = 1）或单一中度或重度创伤性脑损伤（n = 4），以及来自先前证实患有阿尔茨海默病神经病理学变化的患者（n = 6）和没有已知暴露于创伤性脑损伤的材料。对代表性切片进行过度磷酸化或阿尔茨海默病构象选择性tau染色，然后鉴定并绘制典型的神经元缠结和刺状星形胶质细胞。慢性创伤性脑病神经病理改变中棘状星形胶质细胞优先向脑沟深处分布[棘状星形胶质细胞脑沟深/脑回嵴比值为12.84 ± 15.47（平均值±标准差）]，在非运动性损伤患者的材料中，这种病理学比那些暴露于运动相关创伤性脑损伤的患者更明显（P = 0.009）。与此相反，慢性创伤性脑病神经病理改变中的神经纤维缠结在过度磷酸化染色的切片中显示出更均匀的分布。（神经元缠结的沟深与脑回嵴的比率为1.40 ± 0.74）或阿尔茨海默病构象tau（脑沟深度与脑回嵴比值为1.64 ± 1.05），与已知阿尔茨海默病神经病理学改变患者的材料相当（分别为P = 0.82和P = 0.91）。我们的数据表明，在慢性创伤性脑病的神经病理变化的星形胶质细胞成分单独显示优先分布的深度皮质沟。而慢性创伤性脑病的神经元病理改变从脑回嵴到脑沟深度分布较均匀，与阿尔茨海默病的神经元病理改变相呼应。这些观察结果为慢性创伤性脑病的神经病理学特征提供了新的见解，这些特征将其与其他tau病理学区分开来，并表明目前的诊断标准可能需要审查和完善。绘制导致慢性创伤性脑病神经病理变化的病理特征性皮质病变的过度磷酸化tau蛋白病理显示免疫反应性星形胶质细胞优先集中于脑沟深处。相比之下，神经元缠结显示出有限的脑沟集中，与阿尔茨海默病相当。这些数据为慢性创伤性脑病的具体病理提供了新的见解。
Current diagnostic criteria for the neuropathological evaluation of the traumatic brain injury-associated neurodegeneration, chronic traumatic encephalopathy, define the pathognomonic lesion as hyperphosphorylated tau-immunoreactive neuronal and astroglial profiles in a patchy cortical distribution, clustered around small vessels and showing preferential localization to the depths of sulci. However, despite adoption into diagnostic criteria, there has been no formal assessment of the cortical distribution of the specific cellular components defining chronic traumatic encephalopathy neuropathologic change. To address this, we performed comprehensive mapping of hyperphosphorylated tau-immunoreactive neurofibrillary tangles and thorn-shaped astrocytes contributing to chronic traumatic encephalopathy neuropathologic change. From the Glasgow Traumatic Brain Injury Archive and the University of Pennsylvania Center for Neurodegenerative Disease Research Brain Bank, material was selected from patients with known chronic traumatic encephalopathy neuropathologic change, either following exposure to repetitive mild (athletes n = 17; non-athletes n = 1) or to single moderate or severe traumatic brain injury (n = 4), together with material from patients with previously confirmed Alzheimer’s disease neuropathologic changes (n = 6) and no known exposure to traumatic brain injury. Representative sections were stained for hyperphosphorylated or Alzheimer’s disease conformation-selective tau, after which stereotypical neurofibrillary tangles and thorn-shaped astrocytes were identified and mapped. Thorn-shaped astrocytes in chronic traumatic encephalopathy neuropathologic change were preferentially distributed towards sulcal depths [sulcal depth to gyral crest ratio of thorn-shaped astrocytes 12.84 ± 15.47 (mean ± standard deviation)], with this pathology more evident in material from patients with a history of survival from non-sport injury than those exposed to sport-associated traumatic brain injury (P = 0.009). In contrast, neurofibrillary tangles in chronic traumatic encephalopathy neuropathologic change showed a more uniform distribution across the cortex in sections stained for either hyperphosphorylated (sulcal depth to gyral crest ratio of neurofibrillary tangles 1.40 ± 0.74) or Alzheimer’s disease conformation tau (sulcal depth to gyral crest ratio 1.64 ± 1.05), which was comparable to that seen in material from patients with known Alzheimer’s disease neuropathologic changes (P = 0.82 and P = 0.91, respectively). Our data demonstrate that in chronic traumatic encephalopathy neuropathologic change the astroglial component alone shows preferential distribution to the depths of cortical sulci. In contrast, the neuronal pathology of chronic traumatic encephalopathy neuropathologic change is distributed more uniformly from gyral crest to sulcal depth and echoes that of Alzheimer’s disease. These observations provide new insight into the neuropathological features of chronic traumatic encephalopathy that distinguish it from other tau pathologies and suggest that current diagnostic criteria should perhaps be reviewed and refined. Mapping hyper-phosphorylated tau pathologies contributing to the pathognomonic cortical lesion of chronic traumatic encephalopathy neuropathologic change reveals immunoreactive astrocytes preferentially concentrate to sulcal depths. In contrast, neurofibrillary tangles show limited sulcal concentration, comparable with Alzheimer’s disease. These data provide new insight into the specific pathology of chronic traumatic encephalopathy.
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影响因子：
17.1
作者：
Goldstein LE;Fisher AM;Tagge CA;Zhang XL;Velisek L;Sullivan JA;Upreti C;Kracht JM;Ericsson M;Wojnarowicz MW;Goletiani CJ;Maglakelidze GM;Casey N;Moncaster JA;Minaeva O;Moir RD;Nowinski CJ;Stern RA;Cantu RC;Geiling J;Blusztajn JK;Wolozin BL;Ikezu T;Stein TD;Budson AE;Kowall NW;Chargin D;Sharon A;Saman S;Hall GF;Moss WC;Cleveland RO;Tanzi RE;Stanton PK;McKee AC
通讯作者：
McKee AC
影响因子：
3.2
作者：
Doherty, Colin P.;O'Keefe, Eoin;Campbell, Matthew
通讯作者：
Campbell, Matthew
影响因子：
14.5
作者：
Arena, John D.;Smith, Douglas H.;Johnson, Victoria E.
通讯作者：
Johnson, Victoria E.
DOI：
10.1111/j.1365-2990.1996.tb00840.x
发表时间：
1996-02-01
影响因子：
5
作者：
Geddes, JF;Vowles, GH;Sutcliffe, JC
通讯作者：
Sutcliffe, JC
影响因子：
2.5
作者：
GENTLEMAN, SM;ALLSOP, D;ROBERTS, GW
通讯作者：
ROBERTS, GW