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Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype

Janelidze, Shorena LU ; Hertze, Joakim LU ; Nägga, Katarina LU ; Nilsson, Karin; Nilsson, Christer LU ; Wennström, Malin LU ; van Westen, Danielle LU ; Blennow, Kaj LU ; Zetterberg, Henrik LU and Hansson, Oskar LU (2017) In Neurobiology of Aging 51. p.104-112
Abstract

Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls. However, this measure was not changed during preclinical or prodromal Alzheimer's disease and was not associated with amyloid positron emission tomography or APOE genotype. The Qalb was... (More)

Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls. However, this measure was not changed during preclinical or prodromal Alzheimer's disease and was not associated with amyloid positron emission tomography or APOE genotype. The Qalb was increased in diabetes mellitus and correlated positively with CSF biomarkers of angiogenesis and endothelial dysfunction (vascular endothelial growth factor, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1). In healthy elderly, high body mass index and waist-hip ratio predicted increased Qalb 20 years later. In summary, BBB permeability is increased in major dementia disorders but does not relate to amyloid pathology or APOE genotype. Instead, BBB impairment may be associated with diabetes and brain microvascular damage.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amyloid, APOE ε4, Blood-brain barrier, Dementia, Diabetes, Vascular pathology
in
Neurobiology of Aging
volume
51
pages
9 pages
publisher
Elsevier
external identifiers
  • scopus:85007609372
  • wos:000397168600011
ISSN
0197-4580
DOI
10.1016/j.neurobiolaging.2016.11.017
language
English
LU publication?
yes
id
ab5978cb-ead1-41d4-a770-debde7f827a6
date added to LUP
2017-01-13 11:38:15
date last changed
2018-01-13 03:00:08
@article{ab5978cb-ead1-41d4-a770-debde7f827a6,
  abstract     = {<p>Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls. However, this measure was not changed during preclinical or prodromal Alzheimer's disease and was not associated with amyloid positron emission tomography or APOE genotype. The Qalb was increased in diabetes mellitus and correlated positively with CSF biomarkers of angiogenesis and endothelial dysfunction (vascular endothelial growth factor, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1). In healthy elderly, high body mass index and waist-hip ratio predicted increased Qalb 20 years later. In summary, BBB permeability is increased in major dementia disorders but does not relate to amyloid pathology or APOE genotype. Instead, BBB impairment may be associated with diabetes and brain microvascular damage.</p>},
  author       = {Janelidze, Shorena and Hertze, Joakim and Nägga, Katarina and Nilsson, Karin and Nilsson, Christer and Wennström, Malin and van Westen, Danielle and Blennow, Kaj and Zetterberg, Henrik and Hansson, Oskar},
  issn         = {0197-4580},
  keyword      = {Amyloid,APOE ε4,Blood-brain barrier,Dementia,Diabetes,Vascular pathology},
  language     = {eng},
  month        = {03},
  pages        = {104--112},
  publisher    = {Elsevier},
  series       = {Neurobiology of Aging},
  title        = {Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype},
  url          = {http://dx.doi.org/10.1016/j.neurobiolaging.2016.11.017},
  volume       = {51},
  year         = {2017},
}