Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP‐17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer’s disease
Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP‐17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer’s disease
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DOI：
10.1111/j.1365-2990.2006.00736.x
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发表时间：
2006-08
影响因子：
5
通讯作者：
A. Shiarli;R. Jennings;J. Shi;K. Bailey;Y. Davidson;J. Tian;E. Bigio;B. Ghetti;J. Murrell;M. Delisle;S. Mirra;B. Crain;P. Zolo;K. Arima;E. Iseki;S. Murayama;H. Kretzschmar;M. Neumann;C. Lippa;G. Halliday;J. Mackenzie;N. Khan;R. Ravid;D. Dickson;Z. Wszolek;T. Iwatsubo;S. Pickering-Brown;D. Mann
中科院分区：
文献类型：
--
作者：
A. Shiarli;R. Jennings;J. Shi;K. Bailey;Y. Davidson;J. Tian;E. Bigio;B. Ghetti;J. Murrell;M. Delisle;S. Mirra;B. Crain;P. Zolo;K. Arima;E. Iseki;S. Murayama;H. Kretzschmar;M. Neumann;C. Lippa;G. Halliday;J. Mackenzie;N. Khan;R. Ravid;D. Dickson;Z. Wszolek;T. Iwatsubo;S. Pickering-Brown;D. Mann
为了解额颞叶变性(FTLD)的发病机制，对34例伴有12种tau基因突变的17号染色体连锁的额颞叶痴呆(FTDP-17)、11例伴有Pick小体的散发性FTLD和25例早发性阿尔茨海默病(EOAD)患者的额叶皮质平均tau负荷进行了比较。通过使用磷酸依赖抗体AT8、AT100和AT180的免疫组织化学染色切片的图像分析，确定tau负荷，作为染色产物所占组织的百分比。对于AT8和AT180抗体，FTDP-17和散发性FTLD的tau含量(分别为8.5%和10.0%)均显著低于EOAD(分别为16.1%和10.0%)(P均<0.001)。使用AT100，在FTDP-17中检测到的tau的数量是Eoad中检测到的tau的54%(P&0.001)，但在使用这种特定抗体的具有Pick小体的零星FTLD中没有检测到tau。在FTDP-17中，脑内沉积的不溶性tau的数量与MAPT突变在基因中的位置或突变产生的生理或结构变化没有任何系统的关系，无论使用的是哪种抗tau抗体。在这三种疾病中，沉积在大脑中的tau不仅数量不同，而且tau的磷酸化模式也因疾病而异。这些发现提出了与聚集的tau在神经退化中的作用有关的重要问题-这是代表促进神经元存活的适应性反应，还是直接或间接导致受影响细胞退化的有害变化。
In order to gain insight into the pathogenesis of frontotemporal lobar degeneration (FTLD), the mean tau load in frontal cortex was compared in 34 patients with frontotemporal dementia linked to chromosome 17 (FTDP‐17) with 12 different mutations in the tau gene (MAPT), 11 patients with sporadic FTLD with Pick bodies and 25 patients with early onset Alzheimer’s disease (EOAD). Tau load was determined, as percentage of tissue occupied by stained product, by image analysis of immunohistochemically stained sections using the phospho‐dependent antibodies AT8, AT100 and AT180. With AT8 and AT180 antibodies, the amount of tau was significantly (P < 0.001 in each instance) less than that in EOAD for both FTDP‐17 (8.5% and 10.0% respectively) and sporadic FTLD with Pick bodies (16.1% and 10.0% respectively). With AT100, the amount of tau detected in FTDP‐17 was 54% (P < 0.001) of that detected in EOAD, but no tau was detected in sporadic FTLD with Pick bodies using this particular antibody. The amount of insoluble tau deposited within the brain in FTDP‐17 did not depend in any systematic way upon where the MAPT mutation was topographically located within the gene, or on the physiological or structural change generated by the mutation, regardless of which anti‐tau antibody was used. Not only does the amount of tau deposited in the brain differ between the three disorders, but the pattern of phosphorylation of tau also varies according to disease. These findings raise important questions relating to the role of aggregated tau in neurodegeneration – whether this represents an adaptive response which promotes the survival of neurones, or whether it is a detrimental change that directly, or indirectly, brings about the demize of the affected cell.