title: APOE4 predicts amyloid-β in cortical brain biopsy but not idiopathic normal pressure hydrocephalus.
abstract: OBJECTIVE
  To investigate the association of apolipoprotein E (APOE) genotype, especially the APOE4 allele, to (1) idiopathic normal pressure hydrocephalus (iNPH) and (2) amyloid-β (Aβ) plaques in cortical brain biopsies of presumed NPH patients with and without a final clinical diagnosis of Alzheimer's disease (AD).
  
  
  METHODS
  202 patients with presumed NPH were evaluated by intraventricular pressure monitoring and frontal cortical biopsy immunostained against Aβ (134 semiquantified by Aβ plaques/mm2). The 202 patients and 687 cognitively healthy individuals were genotyped for APOE. The final clinical diagnoses in a median follow-up of 3.9 years were: 113 iNPH (94 shunt responsive, 16 shunt non-responsive, three not shunted); 36 AD (12 mixed iNPH + AD); 53 others.
  
  
  RESULTS
  The APOE genotypes distributed similarly in the 94 shunt responsive and 16 non-responsive iNPH patients and healthy controls. In multivariate analysis, the APOE4 allele correlated independently with Aβ plaques in the cortical biopsies (OR 8.7, 95% CI 3.6 to 20, p<0.001). The APOE4 allele in presumed NPH predicted later AD as follows: sensitivity 61%; specificity 77%; positive predictive value 37%; negative predictive value 90%.
  
  
  CONCLUSIONS
  In presumed NPH patients, APOE4 associates independently with the presence of Aβ plaques in the frontal cortical biopsy. APOE4 is not a risk factor for iNPH and does not predict the response to shunt. Our data further support the view that the iNPH syndrome is a distinct dementing disease.
  
  
  BACKGROUND
  Kuopio NPH Registry (http://www.uef.fi/nph).
authors.affiliation: Neurosurgery of NeuroCentre, Kuopio University Hospital, P.O. box 1777, 70211 Kuopio, Finland. okko.pyykko@gmail.com
authors.forename: Okko T
authors.initials: OT
authors.lastname: Pyykkö
authors.forename: Seppo
authors.initials: S
authors.lastname: Helisalmi
authors.forename: Anne M
authors.initials: AM
authors.lastname: Koivisto
authors.forename: Juhani A A
authors.initials: JA
authors.lastname: Mölsä
authors.forename: Jaana
authors.initials: J
authors.lastname: Rummukainen
authors.forename: Ossi
authors.initials: O
authors.lastname: Nerg
authors.forename: Irina
authors.initials: I
authors.lastname: Alafuzoff
authors.forename: Sakari
authors.initials: S
authors.lastname: Savolainen
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Juha E
authors.initials: JE
authors.lastname: Jääskeläinen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Rinne
authors.forename: Ville
authors.initials: V
authors.lastname: Leinonen
authors.forename: Mikko
authors.initials: M
authors.lastname: Hiltunen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D001706:Biopsy; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000235:genetics* / Q000473:pathology; D011237:Predictive Value of Tests; D012042:Registries / Q000706:statistics & numerical data*; D012680:Sensitivity and Specificity; D017287:Ventriculoperitoneal Shunt / Q000706:statistics & numerical data
chemical_list: D001057:Apolipoproteins E