Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Blood-brain barrier transcytosis genes, risk of dementia and stroke: a prospective cohort study of 74,754 individuals

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Copenhagen Baby Heart Study: a population study of newborns with prenatal inclusion

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. The Danish Medical Birth Register

    Research output: Contribution to journalReviewResearchpeer-review

  3. The interaction between smoking and HLA genes in multiple sclerosis: replication and refinement

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Early Life Exposures to Perfluoroalkyl Substances in Relation to Adipokine Hormone Levels at Birth and During Childhood

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Impact of LDL Cholesterol on Microvascular Versus Macrovascular Disease: A Mendelian Randomization Study

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Residual vascular risk in diabetes - Will the SPPARM alpha concept hold the key?

    Research output: Contribution to journalReviewResearchpeer-review

  4. Low LDL Cholesterol by PCSK9 Variation Reduces Cardiovascular Mortality

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

To test whether genetic variants in PICALM, BIN1, CD2AP, and RIN3-suggested to be involved in blood-brain barrier amyloid-β transcytosis pathways-associate with Alzheimer's disease, all dementia, suggested vascular dementia, and stroke, and whether such associations are independent of the strong ε4 APOE risk allele. In a prospective cohort study of 74,754 individuals from the general population we genotyped PICALM (rs10792832), BIN1 (rs6733839), CD2AP (rs10948363), and RIN3 (rs10498633), and generated a weighted and a simple allele score. Multifactorially adjusted hazard ratios for the fourth quartile versus the first quartile of the weighted allele score were 1.42 (95% confidence interval 1.22-1.64) for Alzheimer's disease, and 1.33 (1.19-1.48) for all dementia. For suggested vascular dementia and stroke the corresponding estimates were 1.71 (1.18-2.49) and 1.12 (1.04-1.22), respectively. Hazard ratios were similar after APOE adjustment. Genetic variants in PICALM, BIN1, CD2AP, and RIN3 are associated with increased risk of Alzheimer's disease, all dementia, and suggested vascular dementia independent of the strong APOE ε4 allele. These findings may suggest that clathrin-mediated endocytosis in clearance of amyloid-β across the blood-brain barrier is important for the integrity of both brain tissue and cerebral vessels.

Original languageEnglish
JournalEuropean Journal of Epidemiology
Volume34
Issue number6
Pages (from-to)579-590
Number of pages12
ISSN0393-2990
DOIs
Publication statusPublished - Jun 2019

ID: 57246381