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Association of Plasma Claudin-5 with Age and Alzheimer Disease.

Keisuke TachibanaRyuichi HirayamaNaoyuki SatoKotaro HattoriTakashi KatoHiroyuki TakedaMasuo Kondoh
Published in: International journal of molecular sciences (2024)
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.
Keyphrases
  • mild cognitive impairment
  • cognitive decline
  • endothelial cells
  • blood brain barrier
  • high throughput
  • cerebrospinal fluid
  • high resolution
  • brain injury
  • amino acid
  • single cell
  • single molecule
  • subarachnoid hemorrhage