PT  - JOURNAL ARTICLE
AU  - Okko T Pyykkö
AU  - Seppo Helisalmi
AU  - Anne M Koivisto
AU  - Juhani A A Mölsä
AU  - Jaana Rummukainen
AU  - Ossi Nerg
AU  - Irina Alafuzoff
AU  - Sakari Savolainen
AU  - Hilkka Soininen
AU  - Juha E Jääskeläinen
AU  - Jaakko Rinne
AU  - Ville Leinonen
AU  - Mikko Hiltunen
TI  - APOE4 predicts amyloid-β in cortical brain biopsy but not idiopathic normal pressure hydrocephalus
AID  - 10.1136/jnnp-2011-303849
DP  - 2012 Nov 01
TA  - Journal of Neurology, Neurosurgery & Psychiatry
PG  - 1119--1124
VI  - 83
IP  - 11
4099  - http://jnnp.bmj.com/content/83/11/1119.short
4100  - http://jnnp.bmj.com/content/83/11/1119.full
SO  - J Neurol Neurosurg Psychiatry2012 Nov 01; 83
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)