Worldwide, around 50 million people have dementia. Alzheimer’s disease (AD) is the most common type of dementia and one of the major causes of disability and dependency among the elderly worldwide. Clinically, AD is characterized by impaired memory accompanied by other deficiencies in the cognitive domain. Neuritic plaques (NPs) and neurofibrillary tangles (NFTs) are histopathological lesions that define brains with AD. NFTs consist of abundant intracellular paired helical filaments (PHFs) whose main constituent is tau protein. Tau undergoes posttranslational changes including hyperphosphorylation and truncation, both of which favor conformational changes in the protein. The sequential pathological processing of tau is illustrated with the following specific markers: pT231, TG3, AT8, AT100, and Alz50. Two proteolysis sites for tau have been described—truncation at glutamate 391 and at aspartate 421—and which can be demonstrated by reactivity with the antibodies 423 and TauC-3, respectively. In this review, we describe the molecular changes in tau protein as pre-NFTs progress to extracellular NFTs and during which the formation of a minimal nucleus of the filament, as the PHF core, occurs. We also analyzed the PHF core as the initiator of PHFs and tau phosphorylation as a protective neuronal mechanism against the assembly of the PHF core.

在世界范围内，约有5000万人患有痴呆症。阿尔茨海默氏病（AD）是最常见的痴呆类型，并且是全球老年人中残疾和依赖的主要原因之一。临床上，AD的特征是记忆力减退，并伴有认知领域的其他缺陷。神经性斑块（NP）和神经原纤维缠结（NFT）是定义AD​​的大脑的组织病理学病变。NFT由丰富的细胞内成对螺旋丝（PHF）组成，其主要成分是tau蛋白。Tau经历了翻译后的变化，包括过度磷酸化和截短，这两者都有助于蛋白质的构象变化。用以下特定标记说明tau的顺序病理过程：pT231，TG3，AT8，AT100和Alz50。已经描述了tau的两个蛋白水解位点-在谷氨酸391和天冬氨酸421处的截短-可以分别通过与抗体423和TauC-3的反应来证明。在这篇综述中，我们描述了tau蛋白的分子变化，因为前NFT逐渐发展到细胞外NFT，在此过程中发生了细丝最小核的形成，即PHF核。我们还分析了作为PHFs引发剂的PHF核心，以及tau磷酸化作为针对PHF核心组装的保护性神经元机制。我们描述了tau蛋白的分子变化，随着pre-NFTs前进到细胞外NFTs，在此过程中发生了细丝最小核的形成，即PHF核。我们还分析了作为PHFs引发剂的PHF核心，以及tau磷酸化作为针对PHF核心组装的保护性神经元机制。我们描述了tau蛋白的分子变化，随着pre-NFTs前进到细胞外NFTs，在此过程中发生了细丝最小核的形成，即PHF核。我们还分析了作为PHFs引发剂的PHF核心，以及tau磷酸化作为针对PHF核心组装的保护性神经元机制。