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APOE4 predicts amyloid-β in cortical brain biopsy but not idiopathic normal pressure hydrocephalus
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2012 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 83, no 11, 1119-1124 p.Article in journal (Refereed) Published
Abstract [en]

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/mm 2). 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.

Place, publisher, year, edition, pages
2012. Vol. 83, no 11, 1119-1124 p.
Keyword [en]
amyloid beta protein, apolipoprotein E2, apolipoprotein E3, apolipoprotein E4, adult, age distribution, aged, Alzheimer disease, amyloid plaque, apolipoprotein E4 gene, article, brain biopsy, brain ventricle peritoneum shunt, controlled study, differential diagnosis, disease marker, female, follow up, gait disorder, gene, genetic association, genotype, heterozygote, human, immunohistochemistry, immunoreactivity, intracranial pressure monitoring, major clinical study, male, memory disorder, normotensive hydrocephalus, predictive value, priority journal, sensitivity and specificity, sex difference, treatment response
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-184950DOI: 10.1136/jnnp-2011-303849ISI: 000309813600020OAI: oai:DiVA.org:uu-184950DiVA: diva2:570352
Available from: 2012-11-19 Created: 2012-11-15 Last updated: 2012-11-27Bibliographically approved

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Alafuzoff, Irina
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Molecular and Morphological Pathology
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