Early frontotemporal dementia targets neurons unique to apes and humans
Early frontotemporal dementia targets neurons unique to apes and humans
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DOI：
10.1002/ana.21055
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发表时间：
2006-12-01
影响因子：
11.2
通讯作者：
DeArmond, Stephen J.
中科院分区：
文献类型：
--
作者：
Seeley, William W.;Carlin, Danielle A.;DeArmond, Stephen J.
目的：额颞叶痴呆（Frontotemporal dementia，FTD）是一种严重影响人类社会行为和情感的神经退行性疾病。这种疾病的特征是前扣带回和额岛皮质的早期损伤。这些区域，虽然通常被认为在胚胎发育中是古老的，但却是von Economo神经元（VEN）的专属家园，VEN是一种仅在类人猿和人类中发现的大型双极投射神经元。尽管朝着了解FTD的遗传和分子基础的进展，没有一类选择性脆弱的神经元已被identified.Methods：使用无偏体视学，我们量化的前扣带回VENs和相邻的第5层神经元在FTD（n = 7），阿尔茨海默氏病（n = 5），和年龄匹配的nonneurological控制科目（n = 7）。神经元形态学和免疫组化染色模式提供了进一步的信息VEN susceptibility.Results：FTD与早期，严重，选择性VEN损失，包括减少74%的VEN每节与对照组相比。VEN脱落不归因于一般神经元丢失，并且在FTD病理亚型中观察到。存活的VEN通常是畸形的，在皮克病中有病理性tau蛋白积累。相比之下，阿尔茨海默病患者显示正常的VEN计数和形态，尽管广泛的局部神经病理学。解释：VEN损失链接FTD其签名区域模式。这些发现为理解进化如何使人类大脑容易受到特定形式的退行性疾病的影响提供了一个新的框架。
Objective: Frontotemporal dementia (FTD) is a neurodegenerative disease that erodes uniquely human aspects of social behavior and emotion. The illness features a characteristic pattern of early injury to anterior cingulate and frontoinsular cortex. These regions, though often considered ancient in phylogeny, are the exclusive homes to the von Economo neuron (VEN), a large bipolar projection neuron found only in great apes and humans. Despite progress toward understanding the genetic and molecular bases of FTD, no class of selectively vulnerable neurons has been identified.Methods: Using unbiased stereology, we quantified anterior cingulate VENs and neighboring Layer 5 neurons in FTD (n = 7), Alzheimer's disease (n = 5), and age-matched nonneurological control subjects (n = 7). Neuronal morphology and immunohistochemical staining patterns provided further information about VEN susceptibility.Results: FTD was associated with early, severe, and selective VEN losses, including a 74% reduction in VENs per section compared with control subjects. VEN dropout was not attributable to general neuronal loss and was seen across FTD pathological subtypes. Surviving VENs were often dysmorphic, with pathological tau protein accumulation in Pick's disease. In contrast, patients with Alzheimer's disease showed normal VEN counts and morphology despite extensive local neurofibrillary pathology.Interpretation: VEN loss links FTD to its signature regional pattern. The findings suggest a new framework for understanding how evolution may have rendered the human brain vulnerable to specific forms of degenerative illness.