Laboratory of Neuropathology, Institute of Pathology, Center for Clinical Research, University of Ulm, Germany.
Acta Neuropathol. 2011 Nov;122(5):577-89. doi: 10.1007/s00401-011-0871-6. Epub 2011 Sep 21.
Granulovacuolar degeneration (GVD) is characterized by the presence of vacuolar cytoplasmic lesions in nerve cells of the medial temporal lobe. These changes occur in older non-diseased individuals as well as in patients with Alzheimer's disease (AD), progressive supranuclear palsy (PSP), Pick's, sporadic Parkinson's (PD), and Guam diseases. We stained representative paraffin sections from all parts of the brain with anti-pTDP43, anti-CK1δ or anti-CK1ε from 14 non-demented elderly, 19 AD, 17 non-AD tauopathy, 9 sporadic PD, and 5 TDP43-proteinopathy [amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD)] cases. Our results showed five stages of GVD based on its distribution pattern: GVD began in the hippocampal subfields CA1, CA2, and the subiculum. In a second stage, entorhinal cortex, and CA4 neurons exhibited GVD. Additional neurons were involved in the temporal neocortex in stage 3, whereas the affection of the amygdala and/or the hypothalamus marked stage 4. A fifth and final stage was characterized by additional GVD in the cingulate cortex and occasionally in the frontal and parietal cortices as well as in the oral raphe and pedunculopontine tegmental nuclei. The GVD stages correlated with neurofibrillary tangle stages, Consortium to Establish a Registry for AD (CERAD) scores for neuritic plaque pathology, amyloid β-protein deposition phases, cerebral amyloid angiopathy stages, and clinical dementia rating (CDR) scores. No associations were seen between GVD stage and the presence of non-AD tauopathies, PD, ALS, or FTLD cases. In conclusion, GVD affects neurons in a hierarchical sequence that allows the distinction of five stages. The topographic distribution of GVD restricted to regions involved in response to chronic stress could indicate a link between GVD and chronically stressful influences. Moreover, the association of the GVD stages with those of AD-related pathology but not with other neurodegenerative disorders points to a possible role of GVD and the response to chronic stress in the pathogenesis of AD.
颗粒空泡变性（GVD）的特征是在中颞叶神经细胞中存在空泡细胞质病变。这些变化发生在年龄较大的非患病个体以及阿尔茨海默病（AD）、进行性核上性麻痹（PSP）、皮克氏病、散发性帕金森病（PD）和关岛病患者中。我们使用抗 pTDP43、抗 CK1δ 或抗 CK1ε 对来自 14 名非痴呆老年人、19 名 AD、17 名非 AD tau 病、9 名散发性 PD 和 5 名 TDP43-蛋白病（肌萎缩侧索硬化症 [ALS] 和额颞叶变性 [FTLD]）病例的大脑各部位的代表性石蜡切片进行了染色。我们的结果显示，根据 GVD 的分布模式，它分为五个阶段：GVD 首先发生在海马的 CA1、CA2 和下托区。在第二阶段，内嗅皮层和 CA4 神经元出现 GVD。在第三阶段，颞叶新皮层的更多神经元受到影响，而杏仁核和/或下丘脑的受累标志着第四阶段。第五个也是最后一个阶段的特征是扣带回皮层出现更多的 GVD，偶尔在额叶和顶叶皮层以及口腔中缝核和脑桥被盖核也会出现 GVD。GVD 阶段与神经原纤维缠结阶段、建立 AD 登记册联盟（CERAD）用于神经突斑块病理学的评分、β-淀粉样蛋白沉积阶段、脑淀粉样血管病阶段和临床痴呆评定量表（CDR）评分相关。在 GVD 阶段和非 AD tau 病、PD、ALS 或 FTLD 病例之间没有发现相关性。总之，GVD 按照一个分层的顺序影响神经元，从而可以将其分为五个阶段。GVD 的拓扑分布仅限于与慢性应激反应相关的区域，这表明 GVD 与慢性应激影响之间可能存在联系。此外，GVD 阶段与 AD 相关病理的阶段相关，但与其他神经退行性疾病无关，这表明 GVD 和对慢性应激的反应可能在 AD 的发病机制中起作用。
