Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China.
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.
Sci Rep. 2024 Sep 30;14(1):22744. doi: 10.1038/s41598-024-72559-w.
Observational studies have suggested a bidirectional relationship between idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD). However, the causal association between these two neurodegenerative disorders remains unclear. This study aimed to explore the causal relationship between iNPH and AD using a two-sample bidirectional Mendelian randomization (MR) method. Large-scale genome-wide association studies of iNPH (N = 767, N = 375,610) and AD (N = 111,326, N = 677,663) in European individuals were used to screen genetic instruments for MR analysis. Inverse variance-weighted (IVW) method was used as the main analysis, other MR methods and a series of sensitivity analyses were performed to ensure the reliability. In the forward MR analysis, genetic predisposition to iNPH had no effects on the risk of AD development. Likewise, in the reverse MR analysis, AD did not demonstrate a significant causal effect on iNPH. Sensitivity analyses bolstered the reliability of the MR results. Our MR study indicated no genetic evidence supporting a suggestive association between AD and iNPH in either direction, and provided evidence on the dichotomy between true iNPH and neurodegenerative NPH.
观察性研究表明特发性正常压力脑积水（iNPH）和阿尔茨海默病（AD）之间存在双向关系。然而，这两种神经退行性疾病之间的因果关联尚不清楚。本研究旨在使用两样本双向孟德尔随机化（MR）方法探讨 iNPH 和 AD 之间的因果关系。使用欧洲个体的 iNPH（N = 767，N = 375610）和 AD（N = 111326，N = 677663）的大规模全基因组关联研究来筛选用于 MR 分析的遗传工具。反方差加权（IVW）方法被用作主要分析，其他 MR 方法和一系列敏感性分析被用来确保可靠性。在前向 MR 分析中，iNPH 的遗传易感性对 AD 发展的风险没有影响。同样，在反向 MR 分析中，AD 对 iNPH 也没有表现出显著的因果影响。敏感性分析增强了 MR 结果的可靠性。我们的 MR 研究表明，在任何方向上，AD 和 iNPH 之间都没有遗传证据支持提示性关联，并为真正的 iNPH 和神经退行性 NPH 之间的二分法提供了证据。
