Institute of Clinical Medicine -Neurosurgery, University of Eastern Finland and Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland.
Institute of Clinical Medicine -Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
J Alzheimers Dis. 2017;60(3):1077-1085. doi: 10.3233/JAD-170583.
Idiopathic normal pressure hydrocephalus (iNPH) is a late onset, surgically treated progressive brain disease caused by impaired cerebrospinal fluid dynamics and subsequent ventriculomegaly. Comorbid Alzheimer's disease (AD) seems to be frequent in iNPH.
We aim to evaluate the role of AD-related polymorphisms in iNPH.
Overall 188 shunt-operated iNPH patients and 688 controls without diagnosed neurodegenerative disease were included into analysis. Twenty-three single-nucleotide polymorphisms (SNPs FRMD4A [rs7081208_A, rs2446581_A, rs17314229_T], CR1, BIN, CD2AP, CLU, MS4A6A, MS4A4E, PICALM, ABCA7, CD33, INPP5D, HLA_DRB5, EPHA1, PTK2B, CELF1, SORL1, FERMT2, SLC24A, DSG2, CASS4, and NME8) adjusted to APOE were analyzed between groups by using binary logistic regression analysis. Neuroradiological characteristics and AD-related changes in the right frontal cortical brain biopsies were available for further analysis.
Logistic regression analysis adjusted to age, gender, and other SNPs indicated allelic variation of NME8 between iNPH patients and non-demented controls (p = 0.014). The allelic variation of NME8 was not related to the neuropathological changes in the brain biopsies of iNPH patients. However, periventricular white matter changes (p = 0.017) were more frequent in the iNPH patients with the AA-genotype, an identified risk factor of AD.
Our findings increase the evidence that iNPH is characterized by genetic and pathophysiological mechanisms independent from AD. Considering that NME8 plays a role in the ciliary function and displays SNP-related diversity in white matter changes, the mechanisms of NME8 in iNPH and other neurodegenerative processes are worth further study.
特发性正常压力脑积水（iNPH）是一种起病较晚、可通过手术治疗的进行性脑部疾病，由脑脊液动力学受损和随后的脑室扩大引起。合并阿尔茨海默病（AD）似乎在 iNPH 中较为常见。
我们旨在评估 AD 相关多态性在 iNPH 中的作用。
共纳入 188 例接受分流手术的 iNPH 患者和 688 例未诊断为神经退行性疾病的对照者进行分析。分析了 23 个单核苷酸多态性（SNPs FRMD4A [rs7081208_A、rs2446581_A、rs17314229_T]、CR1、BIN、CD2AP、CLU、MS4A6A、MS4A4E、PICALM、ABCA7、CD33、INPP5D、HLA_DRB5、EPHA1、PTK2B、CELF1、SORL1、FERMT2、SLC24A、DSG2、CASS4 和 NME8），并通过二元逻辑回归分析将其与 APOE 进行了调整。还获得了右额皮质脑活检的神经影像学特征和 AD 相关变化，以便进一步分析。
经年龄、性别和其他 SNPs 调整的逻辑回归分析表明，iNPH 患者与非痴呆对照者之间存在 NME8 的等位基因变异（p = 0.014）。NME8 的等位基因变异与 iNPH 患者脑活检的神经病理学变化无关。然而，在携带 AA 基因型的 iNPH 患者中，脑室周围白质变化更为频繁（p = 0.017），AA 基因型是 AD 的一个已知危险因素。
我们的研究结果进一步证明了 iNPH 的特征是独立于 AD 的遗传和病理生理机制。考虑到 NME8 在纤毛功能中起作用，并且在白质变化中显示 SNP 相关多样性，因此值得进一步研究 NME8 在 iNPH 和其他神经退行性过程中的机制。
