title: Effects of Alzheimer's Disease-Associated Risk Loci on Amyloid-β Accumulation in the Brain of Idiopathic Normal Pressure Hydrocephalus Patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Institute of Clinical Medicine - Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.|Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland and Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
authors: Tiina
authors: T
authors: Laiterä
authors: Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors: Jussi
authors: J
authors: Paananen
authors: Institute of Clinical Medicine - Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors: Seppo
authors: S
authors: Helisalmi
authors: Institute of Clinical Medicine - Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.|Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors: Timo
authors: T
authors: Sarajärvi
authors: Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland and Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
authors: Joel
authors: J
authors: Huovinen
authors: Institute of Clinical Medicine - Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors: Marjo
authors: M
authors: Laitinen
authors: Institute of Clinical Medicine - Pathology, University of Eastern Finland and Department of Pathology, Kuopio University Hospital, Kuopio, Finland.|Department of Pathology, Kuopio University Hospital, Kuopio, Finland.
authors: Tuomas
authors: T
authors: Rauramaa
authors: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors: Irina
authors: I
authors: Alafuzoff
authors: Institute of Clinical Medicine - Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors: Anne M
authors: AM
authors: Remes
authors: Institute of Clinical Medicine - Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors: Hilkka
authors: H
authors: Soininen
authors: A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors: Annakaisa
authors: A
authors: Haapasalo
authors: Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland and Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
authors: Juha E
authors: JE
authors: Jääskeläinen
authors: Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland and Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
authors: Ville
authors: V
authors: Leinonen
authors: Institute of Clinical Medicine - Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.|Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors: Mikko
authors: M
authors: Hiltunen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000235:genetics* / Q000473:pathology*; D008297:Male; D019579:Neocortex / Q000378:metabolism* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer’s disease; amyloid-β; apolipoprotein E; genome wide association studies; idiopathic normal pressure hydrocephalus