Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype
Open accessAbstract
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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Qalb is elevated in individuals with preclinical Alzheimer's disease, mild cognitive impairment, Alzheimer's disease without vascular risk factors, and Alzheimer's disease with vascular risk factors.
“Qalb is elevated in individuals with preclinical AD (229), MCI (421), AD without vascular risk factors (287, 545, 546), and AD with vascular risk factors (67, 68, 74, 629).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [287]
The Results (‘The Qalb in dementias’; page unavailable) report higher Qalb in AD patients than controls. The Results (‘Risk factors for abnormal Qalb’; page unavailable) also associate higher Qalb with diabetes in the dementia cohort, but do not separately establish that it is elevated in AD patients with vascular risk factors. This citation is attached to that AD-with-vascular-risk-factors part of the sentence. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIncreased Qalb and CSF-to-serum IgG ratio are observed early in Parkinson's disease patients before dementia.
“Increased Qalb (287, 288, 362, 474) and CSF-to-serum IgG ratio (474) are observed early in PD patients before dementia.”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [287]
The Results (‘The Qalb in dementias’; page not provided) report increased Qalb in a combined dementia with Lewy bodies/Parkinson’s disease with dementia group. They do not establish that Qalb is increased early in Parkinson’s disease before dementia. This source is cited for the Qalb portion of the sentence, not the IgG-ratio portion. (LLM, conf=0.87)
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- Authors
- Janelidze, S., Hertze, J., Nägga, K., Nilsson, K., Nilsson, C., Wennström, M., van Westen, D., Blennow, K., Zetterberg, H., & Hansson, O.
- Affiliations
- Lund University (SE)
- Skåne University Hospital (SE)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Hansson, Oskar
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 51
- Pages
- 104-112
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC5754327
- OpenAlex
- W2560173378
- Cited by
- 237
- References
- 12
- Citations by year
- 2026: 17 · 2025: 28 · 2024: 34 · 2023: 21 · 2022: 27 · 2021: 20 · 2020: 30 · 2019: 29 · 2018: 21 · 2017: 10
- FWCI
- 10.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurobiology of Aging (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- European Research Council (311292)
- Swedish Research Council (K2014-62X-22525-01-4)
- Strategic Research Area MultiPark
- Crafoord Foundation
- Swedish Brain Foundation
- Swedish Alzheimer Foundation
- Torsten Söderberg Foundation
- Skåne Research Hospital
- Greta and Johan Kock Foundation
- Koch’s Foundation
- Swedish federal government
- Medical Training and Research Agreement
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- blood-brain barrier permeability, dementia, diabetes mellitus, Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease dementia, subcortical vascular dementia, frontotemporal dementia, amyloid pathology, APOE genotype, angiogenesis, endothelial dysfunction, vascular endothelial growth factor, intracellular adhesion molecule-1, VCAM-1, body mass index, waist-to-hip ratio
- MeSH terms
- Cell Adhesion Molecule-1, Aged, Aged, 80 and over, Albumins, Apolipoproteins E, Blood-Brain Barrier, Capillary Permeability, Dementia, Diabetes Mellitus, Female, Genotype, Humans, Immunoglobulins, Male, Middle Aged, Serum Albumin, Cohort Studies, Cell Adhesion Molecules, Amyloid beta-Peptides, Vascular Endothelial Growth Factor A
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