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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
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)....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874026/ https://www.ncbi.nlm.nih.gov/pubmed/24386372 http://dx.doi.org/10.1371/journal.pone.0084405 |
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author | Karch, André Manthey, Henrike Ponto, Claudia Hermann, Peter Heinemann, Uta Schmidt, Christian Zerr, Inga |
author_facet | Karch, André Manthey, Henrike Ponto, Claudia Hermann, Peter Heinemann, Uta Schmidt, Christian Zerr, Inga |
author_sort | Karch, André |
collection | PubMed |
description | 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 (Q(Alb)) 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 Q(Alb) 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 Q(Alb) between ApoE genotypes within the present study. Increased Q(Alb) 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). DISCUSSION: 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 Q(Alb) which has been shown to be a good marker for overall BBB integrity but might not reflect all qualities of the barrier. |
format | Online Article Text |
id | pubmed-3874026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38740262014-01-02 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 Karch, André Manthey, Henrike Ponto, Claudia Hermann, Peter Heinemann, Uta Schmidt, Christian Zerr, Inga PLoS One Research Article 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 (Q(Alb)) 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 Q(Alb) 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 Q(Alb) between ApoE genotypes within the present study. Increased Q(Alb) 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). DISCUSSION: 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 Q(Alb) which has been shown to be a good marker for overall BBB integrity but might not reflect all qualities of the barrier. Public Library of Science 2013-12-27 /pmc/articles/PMC3874026/ /pubmed/24386372 http://dx.doi.org/10.1371/journal.pone.0084405 Text en © 2013 Karch et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Karch, André Manthey, Henrike Ponto, Claudia Hermann, Peter Heinemann, Uta Schmidt, Christian Zerr, Inga 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 |
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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874026/ https://www.ncbi.nlm.nih.gov/pubmed/24386372 http://dx.doi.org/10.1371/journal.pone.0084405 |
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