APOE4 predicts amyloid-beta in cortical brain biopsy but not idiopathic normal pressure hydrocephalus

作者：Pyykko Okko T^*; Helisalmi Seppo; Koivisto Anne M; Molsa Juhani A A; Rummukainen Jaana; Nerg Ossi; Alafuzoff Irina; Savolainen Sakari; Soininen Hilkka; Jaaskelainen Juha E; Rinne Jaakko; Leinonen Ville; Hiltunen Mikko

来源：Journal of Neurology Neurosurgery and Psychiatry, 2012, 83(11): 1119-1124.

DOI：10.1136/jnnp-2012-303849

Objective To investigate the association of apolipoprotein E (APOE) genotype, especially the APOE4 allele, to (1) idiopathic normal pressure hydrocephalus (iNPH) and (2) amyloid-beta (A beta) plaques in cortical brain biopsies of presumed NPH patients with and without a final clinical diagnosis of Alzheimer%26apos;s disease (AD). %26lt;br%26gt;Methods 202 patients with presumed NPH were evaluated by intraventricular pressure monitoring and frontal cortical biopsy immunostained against A beta (134 semiquantified by A beta 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. %26lt;br%26gt;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 A beta plaques in the cortical biopsies (OR 8.7, 95% CI 3.6 to 20, p%26lt;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%. %26lt;br%26gt;Conclusion In presumed NPH patients, APOE4 associates independently with the presence of A beta 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.

• 出版日期2012-11