摘要

       嗜银颗粒病 (AgD) 是一种迟发性痴呆，其形态学特征为丰富的神经纤维颗粒 (ArG)。 ArGs 主要存在于角质层的 CA1 亚区、内嗅皮质和经内嗅皮质、杏仁核和下丘脑外侧结节核。我们最近表明异常磷酸化的 tau 蛋白是 ArGs 的主要蛋白质成分，并且在富含 ArGs 的区域中，tau 在多达 80p.100 的神经细胞中过度磷酸化。我们可以证明至少有一部分谷物是在含有高磷化 tau 的神经元的树突和树突侧枝中形成的。含有晶粒的树突的形态表明，在带有 ArG 的神经元中正在发生一个渐进的树突收缩过程。此外，很明显 ArG 的存在不一定与认知能力下降有关。我们对有和没有痴呆的 AgD 病例的研究表明，AgD 是一种进行性神经退行性疾病，在海马结构的前部有早期亚临床病变。在后期阶段，海马结构的更多尾部部分的参与通常会导致认知能力下降。因此，在一些患有 AgD 的受试者中观察到的痴呆症的一种可能解释是，在整个海马 - 内嗅/海马旁复合体和杏仁核中，突触后结构（包括突触接触）更广泛地丧失。大多数报告的 AgD 病例都与神经原纤维病变（例如神经原纤维缠结）有关，这也是阿尔茨海默病 (AD) 的典型特征。然而，神经原纤维变化不会超过早期（内嗅和边缘）Braak 阶段，这通常与认知能力下降无关。 AgD 的其他神经病理学特征包括少突胶质细胞 tau 丝状包涵体（卷曲体）、气球状神经元和星形细胞 tau 病理学。 AgD 的临床特征知之甚少。然而，回顾性研究的初步数据表明，在 AgD 中，行为障碍将先于记忆力衰竭和记忆力下降。此外，已经表明 ApoEe4 等位基因不构成发生 AgD 的风险因素。总之，AgD 很可能是一种独特的老年痴呆症，必须与其他 tauopathies 区分开来，例如AD，通过形态学和遗传学标准。

       Argyrophilic grain disease (AgD) is a late-onset dementia morphologically characterized by abundant neuropil grains (ArGs). ArGs are mainly found in the CA1 subfield of the cornu ammonis, entorhinal and transentorhinal cortices, the amygdala and the hypothalamic lateral tuberal nuclei. We have recently shown that abnormally phosphosphorylated tau protein is the main protein constituent of ArGs and that tau is hyperphosphorylated in up to 80p.100 of nerve cels in areas rich in ArGs. We could demonstrate that at least a subset of grains are formed within dendrites and dendritic side-branches of neurons containing hyperphosphylated tau. Morphology of dendrites containing grains suggests that a process of progressive dendritic shrinkage is taking place in neurons bearing ArGs. Furthermore it became apparent that the presence of ArGs is not necessarily associated with a cognitive decline. Our studies on AgD cases with and without dementia suggest that AgD is a progressive neurodegenerative disorder with early subclinical lesions in anterior part of the hippocampal formation. At later stages involvement of more caudal parts of the hippocampal formation generally results in a cognitive decline. Thus, one possible explanation for the dementia observed in some subjects with AgD is that there is a more widepread loss of postsynaptic structures, including synaptic contacts, throughout the hippocampus-entorhinal/parahippocampal complex and the amygdaloid nuclei. Most of the reported AgD cases are associated with neurofibrillary lesions (e.g. neurofibrillary tangles) which are also typical of Alzheimer's disease (AD). However, neurofibrillary changes do not exceed early (entorhinal and limbic) Braak stages which generally are not associated with a cognitive decline. Additional neuropathological features of AgD include oligodendroglial tau filamentous inclusions ( coiled bodies ), ballooned neurons and astrocytic tau pathology. The clinical features of AgD are poorly understood. However, preliminary data from retrospective studies suggest that in AgD behavioural disturbances will precede memory failure and memory decline. Furthermore, it has been shown that the ApoEe4 allele does not constitute a risk factor for the development of AgD. In conclusion it seems very likely that AgD is a distinct dementing disorder of old age that has to be distinguished from other tauopathies, e.g. AD, by both morphological and genetic criteria.

https://europepmc.org/article/med/11965171