Granulovacuolar degeneration (GVD) is a histopathological feature of Alzheimer’s disease (AD) and some non-Alzheimer neurodegenerative diseases. It is also present in the brains of non-demented older adults. GVD is characterized by the presence of intracytoplasmic granule-containing vacuoles in most hippocampal neurons. It affects the neurons in sequential arrangement throughout the brain, which allows its characterization into different stages related to the severity of the disease. The mechanism of GVD formation is still poorly understood and its relationship with Tau structures remains unclear. Immunohistochemistry and ultrastructural examination suggest that GVD is mediated by cellular autophagic mechanisms. Other potential mechanisms related to GVD include protein accumulation caused by cellular defence mechanisms or impaired cellular functions. Several proteins are used as markers of GVD. Antibodies to cytoskeletal proteins and neurofilaments, both phosphorylated and non-phosphorylated forms, are used to stain GVD, the latter of which can be used to determine the nature of the cytoskeletal abnormalities in GVD formation. A link between GVD and microtubule-associated protein of tau was also reported but remains unclear. Previous studies reported neurons containing GVDs in the hippocampus of AD sections. Other neurodegenerative diseases also randomly showed GVDs in the brain. However, these quantitative studies have not demonstrated whether GVD is an essential component of AD or non-AD dementias. In this review, we discuss our previous quantitative results of a retrospective study from 2016 and compare them with the results of older published studies to examine whether GVD is an essential feature of AD dementia or additional neurodegenerative features. We also revisit the pathogenesis and histochemistry profile of this common pathology.

中文翻译：

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颗粒空泡变性是阿尔茨海默病的重要病理组成部分吗？旧研究的发病机制和组织化学综述

颗粒空泡变性 (GVD) 是阿尔茨海默病 (AD) 和一些非阿尔茨海默神经退行性疾病的组织病理学特征。它也存在于非痴呆老年人的大脑中。GVD 的特征是在大多数海马神经元中存在含有胞质内颗粒的空泡。它影响整个大脑中按顺序排列的神经元，这使得其特征化为与疾病严重程度相关的不同阶段。GVD 形成的机制仍然知之甚少，其与 Tau 结构的关系仍不清楚。免疫组织化学和超微结构检查表明 GVD 是由细胞自噬机制介导的。与 GVD 相关的其他潜在机制包括由细胞防御机制或细胞功能受损引起的蛋白质积累。几种蛋白质被用作 GVD 的标志物。细胞骨架蛋白和神经丝的抗体（磷酸化和非磷酸化形式）用于染色 GVD，后者可用于确定 GVD 形成中细胞骨架异常的性质。还报告了 GVD 与微管相关 tau 蛋白之间的联系，但仍不清楚。先前的研究报告了 AD 切片海马中含有 GVD 的神经元。其他神经退行性疾病也在大脑中随机显示 GVD。然而，这些定量研究并未证明 GVD 是否是 AD 或非 AD 痴呆的重要组成部分。在这次审查中，我们讨论了 2016 年一项回顾性研究的先前定量结果，并将其与较早发表的研究结果进行比较，以检查 GVD 是 AD 痴呆的基本特征还是其他神经退行性特征。我们还重新审视了这种常见病理的发病机制和组织化学特征。