• Okko T Pyykkö, Seppo Helisalmi, Anne M Koivisto, Juhani A A Mölsä, Jaana Rummukainen, Ossi Nerg, Irina Alafuzoff, Sakari Savolainen, Hilkka Soininen, Juha E Jääskeläinen, Jaakko Rinne, Ville Leinonen, and Mikko Hiltunen.
• Neurosurgery of NeuroCentre, Kuopio University Hospital, P.O. box 1777, 70211 Kuopio, Finland. okko.pyykko@gmail.com
• J. Neurol. Neurosurg. Psychiatr.. 2012 Nov 1;83(11):1119-24.

ObjectiveTo 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).Methods202 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.ResultsThe 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%.ConclusionIn 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 NumberKuopio NPH Registry (http://www.uef.fi/nph).

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