Title | Alzheimer's Disease-Related Polymorphisms in Shunt-Responsive Idiopathic Normal Pressure Hydrocephalus. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Huovinen, J, Helisalmi, S, Paananen, J, Laiterä, T, Kojoukhova, M, Sutela, A, Vanninen, R, Laitinen, M, Rauramaa, T, Koivisto, AM, Remes, AM, Soininen, H, Kurki, M, Haapasalo, A, Jääskeläinen, JE, Hiltunen, M, Leinonen, V |
Journal | J Alzheimers Dis |
Volume | 60 |
Issue | 3 |
Pagination | 1077-1085 |
Date Published | 2017 |
ISSN | 1875-8908 |
Abstract | BACKGROUND: 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. OBJECTIVE: We aim to evaluate the role of AD-related polymorphisms in iNPH. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. |
DOI | 10.3233/JAD-170583 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 28984604 |