Association of Plasma Claudin-5 with Age and Alzheimer Disease

Int J Mol Sci. 2024 Jan 24;25(3):1419. doi: 10.3390/ijms25031419.

Abstract

The blood-brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5-but not pTau181-decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of AD.

Keywords: Alzheimer disease; biomarker; blood–brain barrier; claudin-5; dementia; tight junction.

MeSH terms

  • Alzheimer Disease* / blood
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides
  • Biomarkers
  • Blood-Brain Barrier
  • Claudin-5* / blood
  • Claudin-5* / chemistry
  • Claudin-5* / metabolism
  • Cognitive Dysfunction* / blood
  • Cognitive Dysfunction* / diagnosis
  • Cognitive Dysfunction* / metabolism
  • Endothelial Cells
  • Humans
  • tau Proteins

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Claudin-5
  • tau Proteins