title: Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype.
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 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.
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
authors.forename: Shorena
authors.initials: S
authors.lastname: Janelidze
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Hertze
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Nägga
authors.affiliation: Memory Clinic, Skåne University Hospital, Malmö, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Nilsson
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Department of Neurology, Skåne University Hospital, Lund, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Nilsson
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Wallenberg Laboratory, Malmö, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Wennström
authors.affiliation: Department of Clinical Sciences, Diagnostic radiology, Lund University, Lund, Sweden; Imaging and Function, Skåne University Health Care, Lund, Sweden.
authors.forename: Danielle
authors.initials: D
authors.lastname: van Westen
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden. Electronic address: Oskar.Hansson@med.lu.se.
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D002199:Capillary Permeability; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D003704:Dementia / Q000209:etiology*; D003920:Diabetes Mellitus / Q000097:blood / Q000134:cerebrospinal fluid / Q000209:etiology*; D005260:Female; D005838:Genotype; D006801:Humans; D007136:Immunoglobulins / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin; D042461:Vascular Endothelial Growth Factor A / Q000134:cerebrospinal fluid
chemical_list: D000418:Albumins; D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D012709:Serum Albumin; D042461:Vascular Endothelial Growth Factor A
keywords: APOE ε4; Amyloid; Blood-brain barrier; Dementia; Diabetes; Vascular pathology