BioScience Project, PO Box 352, Wakefield, MA, 01880, USA.
Department of Biotechnology, Chaitanya Bharathi Institute of Technology, Hyderabad, 500075, India.
F1000Res. 2020 Nov 5;9:1299. doi: 10.12688/f1000research.27096.2. eCollection 2020.
People with Down Syndrome (DS) are born with an extra copy of Chromosome (Chr) 21 and many of these individuals develop Alzheimer's Disease (AD) when they age. This is due at least in part to the extra copy of the APP gene located on Chr 21. By 40 years, most people with DS have amyloid plaques which disrupt brain cell function and increase their risk for AD. About half of the people with DS develop AD and the associated dementia around 50 to 60 years of age, which is about the age at which the hereditary form of AD, early onset AD, manifests. In the absence of Chr 21 trisomy, duplication of APP alone is a cause of early onset Alzheimer's disease, making it likely that having three copies of APP is important in the development of AD and in DS. We investigate the relationship between AD and DS through integrative analysis of genesets derived from a MeSH query of AD and DS associated beta amyloid peptides, Chr 21, GWAS identified AD risk factor genes, and differentially expressed genes in individuals with DS. Unique and shared aspects of each geneset were evaluated based on functional enrichment analysis, transcription factor profile and network interactions. Genes that may be important to both disorders in the context of direct association with APP processing, Tau post translational modification and network connectivity are ACSM1, APBA2, APLP1, BACE2, BCL2L, COL18A1, DYRK1A, IK, KLK6, METTL2B, MTOR, NFE2L2, NFKB1, PRSS1, QTRT1, RCAN1, RUNX1, SAP18 SOD1, SYNJ1, S100B. Our findings confirm that oxidative stress, apoptosis, inflammation and immune system processes likely contribute to the pathogenesis of AD and DS which is consistent with other published reports.
唐氏综合征（DS）患者的第 21 号染色体（Chr）存在额外的拷贝，其中许多个体在衰老时会发展为阿尔茨海默病（AD）。这至少部分归因于位于 Chr 21 上的 APP 基因的额外拷贝。到 40 岁时，大多数 DS 患者都有淀粉样斑块，这会破坏脑细胞功能并增加他们患 AD 的风险。大约一半的 DS 患者在 50 到 60 岁左右发展为 AD 和相关痴呆症，这大约是早发性 AD 这种遗传性 AD 形式表现出来的年龄。在没有 Chr 21 三体的情况下，仅 APP 的重复是早发性阿尔茨海默病的原因，这表明 APP 有三个拷贝对于 AD 和 DS 的发展很重要。我们通过对 AD 和 DS 相关的β淀粉样肽、Chr 21、GWAS 确定的 AD 风险因素基因和 DS 个体中差异表达基因进行 MeSH 查询的基因集的综合分析，研究 AD 和 DS 之间的关系。基于功能富集分析、转录因子谱和网络相互作用，评估了每个基因集的独特和共享方面。在与 APP 处理、Tau 翻译后修饰和网络连通性直接相关的背景下，可能对两种疾病都很重要的基因包括 ACSM1、APBA2、APLP1、BACE2、BCL2L、COL18A1、DYRK1A、IK、KLK6、METTL2B、MTOR、NFE2L2、NFKB1、PRSS1、QTRT1、RCAN1、RUNX1、SAP18、SOD1、SYNJ1、S100B。我们的研究结果证实，氧化应激、细胞凋亡、炎症和免疫系统过程可能有助于 AD 和 DS 的发病机制，这与其他已发表的报告一致。
