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).
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).
Authors: Okko T Pyykkö; Miikka Lumela; Jaana Rummukainen; Ossi Nerg; Toni T Seppälä; Sanna-Kaisa Herukka; Anne M Koivisto; Irina Alafuzoff; Lakshman Puli; Sakari Savolainen; Hilkka Soininen; Juha E Jääskeläinen; Mikko Hiltunen; Henrik Zetterberg; Ville Leinonen Journal: PLoS One Date: 2014-03-17 Impact factor: 3.240
Authors: Heikki Lukkarinen; Anna Jeppsson; Carsten Wikkelsö; Kaj Blennow; Henrik Zetterberg; Radu Constantinescu; Anne M Remes; Sanna-Kaisa Herukka; Mikko Hiltunen; Tuomas Rauramaa; Katarina Nägga; Ville Leinonen; Mats Tullberg Journal: Fluids Barriers CNS Date: 2022-02-05
Authors: Joel Räsänen; Joel Huovinen; Ville E Korhonen; Antti Junkkari; Sami Kastinen; Simo Komulainen; Minna Oinas; Cecilia Avellan; Janek Frantzen; Jaakko Rinne; Antti Ronkainen; Mikko Kauppinen; Kimmo Lönnrot; Markus Perola; Anne M Koivisto; Anne M Remes; Hilkka Soininen; Mikko Hiltunen; Seppo Helisalmi; Mitja I Kurki; Juha E Jääskeläinen; Ville Leinonen Journal: Fluids Barriers CNS Date: 2020-09-15