RT Journal Article SR Electronic T1 APOE4 predicts amyloid-β in cortical brain biopsy but not idiopathic normal pressure hydrocephalus JF Journal of Neurology, Neurosurgery & Psychiatry JO J Neurol Neurosurg Psychiatry FD BMJ Publishing Group Ltd SP 1119 OP 1124 DO 10.1136/jnnp-2011-303849 VO 83 IS 11 A1 Okko T Pyykkö A1 Seppo Helisalmi A1 Anne M Koivisto A1 Juhani A A Mölsä A1 Jaana Rummukainen A1 Ossi Nerg A1 Irina Alafuzoff A1 Sakari Savolainen A1 Hilkka Soininen A1 Juha E Jääskeläinen A1 Jaakko Rinne A1 Ville Leinonen A1 Mikko Hiltunen YR 2012 UL http://jnnp.bmj.com/content/83/11/1119.abstract AB 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%. Conclusion 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. Trial registration number Kuopio NPH Registry (http://www.uef.fi/nph)