Swaab D F, Grundke-Iqbal I, Iqbal K, Kremer H P, Ravid R, van de Nes J A
Netherlands Institute for Brain Research, Amsterdam.
Brain Res. 1992 Sep 11;590(1-2):239-49. doi: 10.1016/0006-8993(92)91101-j.
Immunocytochemical staining of hypothalamic cell groups with four antibodies to Alzheimer paired helical filaments (PHF) (i.e., anti-PHF serum 60e and monoclonal antibody (mAb) Alz-50, both directed against normal and abnormally phosphorylated tau; mAb tau-1, which recognizes tau; and mAb 3-39 to PHF, which recognizes the carboxy terminal domain of ubiquitin) revealed a clear distinction between 12 Alzheimer's disease (AD) patients and seven controls in the hypothalamus. Dystrophic neurites, which appeared to be the most specific components in AD, were most conspicuous after Alz-50 staining. However, Alz-50 also stained neuronal cytoplasm and normal, thin, beaded neurites in the paraventricular nucleus (PVN) of controls, even of young cases. This staining was clearly distinct from the staining of cytoplasm and dystrophic neurites in the PVN of Alzheimer patients. The abundant staining of dystrophic neurites and cell bodies in the nucleus tuberalis lateralis (NTL) in AD, in which no neuronal loss is observed, suggests that alterations in cytoskeletal markers do not necessarily indicate impending cell death. Moreover, the cytoskeletal changes in the NTL, sexually dimorphic and suprachiasmatic nuclei in AD indicate that this condition is not restricted to cortical areas or nuclei projecting to the cortex. Consequently, the pathophysiological implications of cytoskeletal staining in AD are at present far from clear. The human hypothalamus may not only provide a better insight into the pathogenesis of Alzheimer's disease, but could also be of help in the neuropathological diagnosis of this condition.
用四种针对阿尔茨海默病配对螺旋丝（PHF）的抗体（即抗PHF血清60e和单克隆抗体（mAb）Alz - 50，二者均针对正常和异常磷酸化的tau；识别tau的mAb tau - 1；以及识别泛素羧基末端结构域的针对PHF的mAb 3 - 39）对下丘脑细胞群进行免疫细胞化学染色，结果显示12例阿尔茨海默病（AD）患者与7例对照者在下丘脑中存在明显差异。营养不良性神经突似乎是AD中最具特异性的成分，在Alz - 50染色后最为明显。然而，Alz - 50也对对照组（甚至年轻病例）室旁核（PVN）中的神经元细胞质以及正常、纤细、串珠状神经突进行染色。这种染色与AD患者PVN中的细胞质和营养不良性神经突的染色明显不同。在无神经元丢失的外侧结节核（NTL）中，AD患者的营养不良性神经突和细胞体大量染色，这表明细胞骨架标志物的改变不一定预示着即将发生的细胞死亡。此外，AD患者NTL、性二态核和视交叉上核中的细胞骨架变化表明，这种情况并不局限于皮质区域或投射到皮质的核团。因此，目前AD中细胞骨架染色的病理生理意义尚不清楚。人类下丘脑不仅可能有助于更好地了解阿尔茨海默病的发病机制，还可能有助于这种疾病的神经病理学诊断。
