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APOE4 predicts amyloid-β in cortical brain biopsy but not idiopathic normal pressure hydrocephalus.
MedLine Citation:
PMID:  22955176     Owner:  NLM     Status:  Publisher    
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. TRIAL REGISTRATION NUMBER: Kuopio NPH Registry (
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; Mikko Hiltunen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-6
Journal Detail:
Title:  Journal of neurology, neurosurgery, and psychiatry     Volume:  -     ISSN:  1468-330X     ISO Abbreviation:  J. Neurol. Neurosurg. Psychiatr.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985191R     Medline TA:  J Neurol Neurosurg Psychiatry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
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