TY - JOUR
T1 - Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype
AU - Janelidze, Shorena
AU - Hertze, Joakim
AU - Nägga, Katarina
AU - Nilsson, Karin
AU - Nilsson, Christer
AU - Wennström, Malin
AU - van Westen, Danielle
AU - Blennow, Kaj
AU - Zetterberg, Henrik
AU - Hansson, Oskar
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - Amyloid
KW - APOE ε4
KW - Blood-brain barrier
KW - Dementia
KW - Diabetes
KW - Vascular pathology
UR - http://www.scopus.com/inward/record.url?scp=85007609372&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2016.11.017
DO - 10.1016/j.neurobiolaging.2016.11.017
M3 - Article
C2 - 28061383
AN - SCOPUS:85007609372
SN - 0197-4580
VL - 51
SP - 104
EP - 112
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -