Granholm Ann-Charlotte, Hamlett Eric D
Department of Neurosurgery, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA.
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
J Clin Med. 2024 Feb 27;13(5):1338. doi: 10.3390/jcm13051338.
: Individuals with Down syndrome (DS) exhibit an almost complete penetrance of Alzheimer's disease (AD) pathology but are underrepresented in clinical trials for AD. The Tau protein is associated with microtubule function in the neuron and is crucial for normal axonal transport. In several different neurodegenerative disorders, Tau misfolding leads to hyper-phosphorylation of Tau (p-Tau), which may seed pathology to bystander cells and spread. This review is focused on current findings regarding p-Tau and its potential to seed pathology as a "prion-like" spreader. It also considers the consequences of p-Tau pathology leading to AD, particularly in individuals with Down syndrome. : Scopus (SC) and PubMed (PM) were searched in English using keywords "tau AND seeding AND brain AND down syndrome". A total of 558 SC or 529 PM potentially relevant articles were identified, of which only six SC or three PM articles mentioned Down syndrome. This review was built upon the literature and the recent findings of our group and others. : Misfolded p-Tau isoforms are seeding competent and may be responsible for spreading AD pathology. : This review demonstrates recent work focused on understanding the role of neurofibrillary tangles and monomeric/oligomeric Tau in the prion-like spreading of Tau pathology in the human brain.
唐氏综合征（DS）患者几乎完全会出现阿尔茨海默病（AD）病理特征，但在AD临床试验中的代表性不足。Tau蛋白与神经元中的微管功能相关，对正常轴突运输至关重要。在几种不同的神经退行性疾病中，Tau蛋白错误折叠会导致Tau蛋白过度磷酸化（p-Tau），这可能会将病理特征传递给旁观者细胞并扩散。本综述聚焦于当前关于p-Tau及其作为“朊病毒样”传播者引发病理特征的潜力的研究结果。它还考虑了p-Tau病理特征导致AD的后果，特别是在唐氏综合征患者中。：使用关键词“tau AND seeding AND brain AND down syndrome”在Scopus（SC）和PubMed（PM）数据库中进行英文检索。共识别出558篇SC或529篇PM可能相关的文章，其中只有6篇SC或3篇PM文章提到了唐氏综合征。本综述基于文献以及我们团队和其他团队的最新研究结果。：错误折叠的p-Tau异构体具有播种能力，可能是AD病理特征传播的原因。：本综述展示了近期致力于理解神经原纤维缠结以及单体/寡聚体Tau在人脑中Tau病理特征的朊病毒样传播中作用的研究工作。
