Effects of Alzheimer's Disease-Associated Risk Loci on Amyloid-β Accumulation in the Brain of Idiopathic Normal Pressure Hydrocephalus Patients
| Autor: | Marjo Laitinen, Jussi Paananen, Seppo Helisalmi, Tuomas Rauramaa, Juha E. Jääskeläinen, Ville Leinonen, Joel Huovinen, Annakaisa Haapasalo, Mikko Hiltunen, Anne M. Remes, Irina Alafuzoff, Timo Sarajärvi, Tiina Laiterä, Hilkka Soininen |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male Pathology medicine.medical_specialty Apolipoprotein E4 Single-nucleotide polymorphism Genome-wide association study Neocortex Polymorphism Single Nucleotide Cohort Studies 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Medicine Humans Allele Genetic association Aged Aged 80 and over Amyloid beta-Peptides business.industry General Neuroscience General Medicine medicine.disease Hydrocephalus Normal Pressure Psychiatry and Mental health Clinical Psychology 030104 developmental biology Female Cerebrospinal fluid pressure Geriatrics and Gerontology Alzheimer's disease Amyloid Precursor Protein Secretases business 030217 neurology & neurosurgery Ventriculomegaly Genome-Wide Association Study |
| Zdroj: | Journal of Alzheimer's disease : JAD. 55(3) |
| ISSN: | 1875-8908 |
| Popis: | Background Idiopathic normal pressure hydrocephalus (iNPH) is a dementing condition featuring characteristic symptoms, ventriculomegaly, and normal or slightly elevated cerebrospinal fluid pressure. In Alzheimer's disease (AD) patients, diffuse aggregates of amyloid-β (Aβ) and neurofibrillary hyperphosphorylated tau are detected in the neocortex of the brain, while similar accumulation of Aβ is also detected in iNPH. Recent genome-wide association studies have identified several novel risk loci for AD, potentially affecting Aβ-related cellular processes. Apart from the apolipoprotein E ɛ4 allele (APOE4), the risk effect of single loci is low, emphasizing the importance of the polygenic risk score approach when assessing the combined effects. Objective To study the effects of AD-associated individual and polygenic risk score of single nucleotide polymorphisms (SNPs) on the accumulation of Aβ in the brain samples of iNPH patients. Methods A sample set of frontal cortex biopsies from 188 iNPH patients were divided into two groups according to the Aβ pathology. After the genotyping of the AD-associated risk loci, polygenic risk score was calculated for each iNPH patient and subsequently analyzed in relation to Aβ deposition. Results Apart from the APOE4, none of the SNPs revealed a statistically significant effect on the accumulation of Aβ in iNPH. Also, the non-APOE4 polygenic risk score did not associate with Aβ deposition. Conclusion Novel AD-associated risk genes have no significant effect on Aβ accumulation in the brain of iNPH patients. However, APOE4 affects the Aβ deposition in the brain of iNPH and AD patients in a similar manner. |
| Databáze: | OpenAIRE |
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