Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Association of Plasma Claudin-5 with Age and Alzheimer Disease

Keisuke Tachibna
ORCID logo ,
Ryuichi Hirayama
,
Naoyuki Sato
,
Kotaro Hattori
,
Takashi Kato
,
Hiroyuki Takeda
ORCID logo ,
Masuo Kondoh
*
Version 1 : Received: 12 November 2023 / Approved: 14 November 2023 / Online: 14 November 2023 (11:27:50 CET)

A peer-reviewed article of this Preprint also exists.

Tachibana, K.; Hirayama, R.; Sato, N.; Hattori, K.; Kato, T.; Takeda, H.; Kondoh, M. Association of Plasma Claudin-5 with Age and Alzheimer Disease. International Journal of Molecular Sciences 2024, 25, 1419, doi:10.3390/ijms25031419. Tachibana, K.; Hirayama, R.; Sato, N.; Hattori, K.; Kato, T.; Takeda, H.; Kondoh, M. Association of Plasma Claudin-5 with Age and Alzheimer Disease. International Journal of Molecular Sciences 2024, 25, 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 by 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 MCI and AD.

Keywords

blood-brain barrier; claudin-5; tight junction; biomarker; dementia; Alzheimer disease

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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