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

• 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.

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)