Linking APOE-ε4, blood-brain barrier dysfunction, and inflammation to Alzheimer's pathology

Joost M. Riphagen*, Inez H. G. M. Ramakers, Whitney M. Freeze, Linda H. G. Pagen, Bernard J. Hanseeuw, Marcel M. Verbeek, Frans R. J. Verhey, Heidi I. L. Jacobs

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Web of Science)

Abstract

The APOE-epsilon 4 genotype is a risk factor for late-onset Alzheimer's disease (AD) as well as vascular pathology. Given the increased risk of blood-brain barrier (BBB) dysfunction and inflammation among APOE-epsilon 4 carriers, we aimed to examine whether BBB dysfunction and inflammation contribute to the relationship between APOE and AD key pathologies, as measured in the cerebrospinal fluid (CSF). We applied bootstrapped regression and path analyses involving Q-albumin CSF/plasma ratio (a BBB/blood-CSF barrier function marker), interleukins (IL-1 beta, IL-6, and IL-12p70; inflammation markers), and CSF p-Tau(181) and amyloid-beta(1-42) (AD pathology markers) of 97 participants (aged 38-83 years) from a university memory clinic. Our results showed that relationship between BBB dysfunction and AD pathology is modulated by IL-6 and these associations appear to be driven by the APOE-epsilon 4 genotype. This suggests that APOE-epsilon 4-related vascular factors are also part of the pathway to AD pathology, in synergy with an elevated immune response, and could become targets for trials focused on delaying AD. (C) 2019 The Author(s). Published by Elsevier Inc.

Original languageEnglish
Pages (from-to)96-103
Number of pages8
JournalNeurobiology of Aging
Volume85
DOIs
Publication statusPublished - Jan 2020

Keywords

  • Alzheimer's disease
  • Inflammation
  • Blood-brain barrier
  • APOE
  • Vascular
  • MILD COGNITIVE IMPAIRMENT
  • CEREBROSPINAL-FLUID
  • SAMPLE-SIZE
  • ASSOCIATION WORKGROUPS
  • DIAGNOSTIC GUIDELINES
  • NATIONAL INSTITUTE
  • DISEASE
  • DEMENTIA
  • INTERLEUKIN-6
  • TAU

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