Elevated cerebrospinal fluid and plasma N-Cadherin in Alzheimer disease

Ji Young Choi, Sun Jung Cho, Jung Hyun Park, Sang Moon Yun, Chulman Jo, Eun Joo Kim, Gi Yeong Huh, Moon Ho Park, Changsu Han, Young Ho Koh

Research output: Contribution to journalArticle

Abstract

N-cadherin is a synaptic adhesion molecule stabilizing synaptic cell structure and function. Cleavage of N-cadherin by c-secretase produces a C-terminal fragment, which is increased in the brains of Alzheimer disease (AD) patients. Here, we investigated the relationship between fluid N-cadherin levels and AD pathology. We first showed that the cleaved levels of N-cadherin were increased in homogenates of postmortem brain from AD patients compared with that in non-AD patients. We found that cleaved N-cadherin levels in the cerebrospinal fluid were increased in AD dementia compared with that in healthy control. ELISA results revealed that plasma levels of N-cadherin in 76 patients with AD were higher than those in 133 healthy control subjects. The N-cadherin levels in the brains of an AD mouse model, APP Swedish/PS1delE9 Tg (APP Tg) were reduced compared with that in control. The N-terminal fragment of N-cadherin produced by cleavage at a plasma membrane was detected extravascularly, accumulated in senile plaques in the cortex of an APP Tg mouse. In addition, N-cadherin plasma levels were increased in APP Tg mice. Collectively, our study suggests that alteration of N-cadherin levels might be associated with AD pathology.

Original languageEnglish
Pages (from-to)484-492
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume79
Issue number5
DOIs
Publication statusPublished - 2020 May 1

Keywords

  • Alzheimer disease
  • Brain
  • Cerebrospinal fluid
  • Dementia
  • N-cadherin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Choi, J. Y., Cho, S. J., Park, J. H., Yun, S. M., Jo, C., Kim, E. J., Huh, G. Y., Park, M. H., Han, C., & Koh, Y. H. (2020). Elevated cerebrospinal fluid and plasma N-Cadherin in Alzheimer disease. Journal of Neuropathology and Experimental Neurology, 79(5), 484-492. https://doi.org/10.1093/jnen/nlaa019