Clinical Neuroanatomy, Center for Biomedical Research, Department of Neurology, University of Ulm, Ulm, Germany.
Neurobiol Aging. 2013 Jan;34(1):286-97. doi: 10.1016/j.neurobiolaging.2012.02.031. Epub 2012 Apr 11.
We identified p62-immunoreactive inclusions in dendrites of catecholaminergic brainstem projection neurons using antibodies against p62, ubiquitin, α-synuclein, hyperphosphorylated tau, and tyrosine hydroxylase in 100-μm sections through the brainstem dorsal vagal area, locus coeruleus, and substantia nigra of 149 autopsy cases staged for intraneuronal Alzheimer's and Parkinson's disease-associated lesions. The inclusions resembled Marinesco bodies within cell nuclei of catecholaminergic neurons as well as the dot-like structures previously described by Dickson in specific neuropil areas in humans. The p62-positive inclusions were confined to dendrites of catecholaminergic neurons, lacked neuromelanin granules, and were tau- and α-synuclein-negative. Their immunoreactivity for ubiquitin varied and their prevalence significantly increased with advancing age. The presence or absence of Alzheimer's and/or Parkinson's disease-associated pathology did not influence their existence. There was a strong association between the presence of p62-positive inclusions and Marinesco bodies (p < 0.0001). Our results reveal a hitherto unknown alteration within specific neuronal types of the human brainstem that may be independent of the sequestosome-ubiquitin-proteasomal pathway and unrelated to proteinaceous aggregate-formation of neurodegenerative diseases.
我们使用针对 p62、泛素、α-突触核蛋白、磷酸化 tau 和酪氨酸羟化酶的抗体，在 149 例尸检病例的脑干背侧迷走神经区、蓝斑和黑质中通过 100μm 切片，鉴定出多巴胺能脑投射神经元树突中的 p62 免疫反应性包含物。这些包含物类似于多巴胺能神经元细胞核内的 Marinesco 体，以及 Dickson 之前在人类特定神经胶状区域描述的点状结构。p62 阳性包含物局限于多巴胺能神经元的树突，缺乏神经黑色素颗粒，tau 和 α-突触核蛋白阴性。它们的泛素免疫反应性不同，随着年龄的增长，其患病率显著增加。阿尔茨海默病和/或帕金森病相关病理学的存在与否并不影响其存在。p62 阳性包含物的存在与 Marinesco 体之间存在强烈关联（p < 0.0001）。我们的结果揭示了人类脑干特定神经元类型中一种迄今未知的改变，这种改变可能独立于自噬体-泛素-蛋白酶体途径，与神经退行性疾病的蛋白聚集形成无关。
