title: Investigating the association of ApoE genotypes with blood-brain barrier dysfunction measured by cerebrospinal fluid-serum albumin ratio in a cohort of patients with different types of dementia.
abstract: BACKGROUND
  Since more than a decade ApoE is known to be a strong risk factor for Alzheimer's disease (AD); however, molecular pathways mediating this risk are still unclear. In recent years it has been hypothesized that ApoE might play a role in the disintegration of blood-brain barrier (BBB). In the present study we addressed the question if ApoE genotypes might be associated with BBB function measured by albumin ratio (QAlb) in a large cohort of patients with different types of dementia.
  
  
  METHODS
  Five hundred twenty (520) patients with Creutzfeldt-Jakob disease (CJD, n = 350), Alzheimer's disease (n = 71) and cerebral small vessel disease (n = 99) were assessed for their ApoE genotype. BBB function was measured in all patients using QAlb and was compared between ApoE genotypes. Dominant and additive genetic models were assumed in order to investigate the potential effect of ApoE on BBB function.
  
  
  RESULTS
  We observed no systematic differences in QAlb between ApoE genotypes within the present study. Increased QAlb levels were shown for those without E3 allele in the subgroup of CJD patients when assuming a dominant genetic model (p = 0.035). This could not be confirmed for patients with other forms of dementia (p = 0.234).
  
  
  CONCLUSIONS
  Although there was some evidence for a protective effect of E3 alleles in CJD patients, this study does not support the hypothesis of a systematic role of ApoE genotypes in BBB function in individuals with a diagnosis of dementia. Thus, changes in BBB function do not seem to contribute to the increased risk of cognitive decline associated with certain ApoE genotypes. The interpretation of the results of this study must take into account that BBB function was only assessed by measuring QAlb which has been shown to be a good marker for overall BBB integrity but might not reflect all qualities of the barrier.
authors.affiliation: Department of Neurology, Clinical Dementia Centre, University Hospital Göttingen, Göttingen, Germany ; Department of Epidemiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Karch
authors.affiliation: Department of Neurology, Clinical Dementia Centre, University Hospital Göttingen, Göttingen, Germany.
authors.forename: Henrike
authors.initials: H
authors.lastname: Manthey
authors.affiliation: Department of Neurology, Clinical Dementia Centre, University Hospital Göttingen, Göttingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ponto
authors.affiliation: Department of Neurology, Clinical Dementia Centre, University Hospital Göttingen, Göttingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hermann
authors.affiliation: Department of Neurology, Clinical Dementia Centre, University Hospital Göttingen, Göttingen, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Heinemann
authors.affiliation: Department of Neurology, Clinical Dementia Centre, University Hospital Göttingen, Göttingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Department of Neurology, Clinical Dementia Centre, University Hospital Göttingen, Göttingen, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D001812:Blood-Brain Barrier; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics*; D015140:Dementia, Vascular / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D012189:Retrospective Studies
chemical_list: D001057:Apolipoproteins E