Wohlfert Abigail J, Phares Jeremiah, Granholm Ann-Charlotte
Department of Modern Human Anatomy and Cell & Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Department of Neurosurgery, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA.
J Clin Med. 2024 Oct 17;13(20):6183. doi: 10.3390/jcm13206183.
Down syndrome (DS) is a chromosomal condition that causes many systemic dysregulations, leading to several possible age-related diseases including Alzheimer's disease (AD). This may be due to the triplication of the Amyloid precursor protein (APP) gene or other alterations in mechanistic pathways, such as the mTOR pathway. Impairments to upstream regulators of mTOR, such as insulin, PI3K/AKT, AMPK, and amino acid signaling, have been linked to amyloid beta plaques (Aβ) and neurofibrillary tangles (NFT), the most common AD pathologies. However, the mechanisms involved in the progression of pathology in human DS-related AD (DS-AD) are not fully investigated to date. Recent advancements in omics platforms are uncovering new insights into neurodegeneration. Genomics, spatial transcriptomics, proteomics, and metabolomics are novel methodologies that provide more data in greater detail than ever before; however, these methods have not been used to analyze the mTOR pathways in connection to DS-AD. Using these new techniques can unveil unexpected insights into pathological cellular mechanisms through an unbiased approach.
唐氏综合征（DS）是一种染色体疾病，会导致许多系统性失调，引发包括阿尔茨海默病（AD）在内的几种可能与年龄相关的疾病。这可能是由于淀粉样前体蛋白（APP）基因的三倍体或其他机制途径的改变，如mTOR途径。mTOR上游调节因子的损伤，如胰岛素、PI3K/AKT、AMPK和氨基酸信号传导，与淀粉样β斑块（Aβ）和神经原纤维缠结（NFT）有关，这是最常见的AD病理特征。然而，迄今为止，人类唐氏综合征相关阿尔茨海默病（DS-AD）病理进展所涉及的机制尚未得到充分研究。组学平台的最新进展正在揭示神经退行性变的新见解。基因组学、空间转录组学、蛋白质组学和代谢组学是新颖的方法，它们能比以往提供更详细、更多的数据；然而，这些方法尚未用于分析与DS-AD相关的mTOR途径。使用这些新技术可以通过无偏见的方法揭示病理细胞机制中意想不到的见解。
