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

NEUROBIOLOGY OF AGING

卷:51

Article

Janelidze, Shorena¹  Hertze, Joakim^1,2  Nagga, Katarina^1,2  Nilsson, Karin²  Nilsson, Christer^1,3  Wennstrom, Malin⁴  van Westen, Danielle^5,6  Blennow, Kaj^7,8  Zetterberg, Henrik^7,8,9  Hansson, Oskar^1,2 

[1] Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden

[2] Skane Univ Hosp, Memory Clin, SE-20502 Malmo, Sweden

[3] Skane Univ Hosp, Dept Neurol, Lund, Sweden

[4] Lund Univ, Clin Memory Res Unit, Dept Clin Sci, Wallenberg Lab, Malmo, Sweden

[5] Lund Univ, Dept Clin Sci, Diagnost Radiol, Lund, Sweden

[6] Skane Univ Hlth Care, Imaging & Funct, Lund, Sweden

[7] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden

[8] Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden

[9] UCL Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England

关键词: Blood-brain barrier;    Dementia;    Amyloid;    APOE epsilon 4;    Diabetes;    Vascular pathology;   

DOI  :  10.1016/j.neurobiolaging.2016.11.017

来源: Elsevier

【 摘 要 】

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 bio-markers 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. (C) 2016 The Authors. Published by Elsevier Inc.

【 授权许可】

Free