Association of Plasma Claudin-5 with Age and Alzheimer Disease
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 pr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/3/1419 |
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| author | Keisuke Tachibana Ryuichi Hirayama Naoyuki Sato Kotaro Hattori Takashi Kato Hiroyuki Takeda Masuo Kondoh |
| author_facet | Keisuke Tachibana Ryuichi Hirayama Naoyuki Sato Kotaro Hattori Takashi Kato Hiroyuki Takeda Masuo Kondoh |
| author_sort | Keisuke Tachibana |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T03:57:10Z |
| format | Article |
| id | doaj.art-e4cec6087619477291dc341157459c98 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T03:57:10Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e4cec6087619477291dc341157459c982024-02-09T15:13:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01253141910.3390/ijms25031419Association of Plasma Claudin-5 with Age and Alzheimer DiseaseKeisuke Tachibana0Ryuichi Hirayama1Naoyuki Sato2Kotaro Hattori3Takashi Kato4Hiroyuki Takeda5Masuo Kondoh6Graduate School of Pharmaceutical Sciences, Osaka University, Suita 565-0871, Osaka, JapanGraduate School of Medicine, Osaka University, Suita 565-0871, Osaka, JapanGraduate School of Medicine, Osaka University, Suita 565-0871, Osaka, JapanDepartment of Bioresources, Medical Genome Center, National Center of Neurology and Psychiatry, Kodaira 187-8551, Tokyo, JapanDepartment of Clinical and Experimental Neuroimaging, National Center for Geriatrics and Gerontology, Obu 474-8511, Aichi, JapanProteo-Science Center, Ehime University, Matsuyama 790-8577, Ehime, JapanGraduate School of Pharmaceutical Sciences, Osaka University, Suita 565-0871, Osaka, JapanThe 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.https://www.mdpi.com/1422-0067/25/3/1419blood–brain barrierclaudin-5tight junctionbiomarkerdementiaAlzheimer disease |
| spellingShingle | Keisuke Tachibana Ryuichi Hirayama Naoyuki Sato Kotaro Hattori Takashi Kato Hiroyuki Takeda Masuo Kondoh Association of Plasma Claudin-5 with Age and Alzheimer Disease International Journal of Molecular Sciences blood–brain barrier claudin-5 tight junction biomarker dementia Alzheimer disease |
| title | Association of Plasma Claudin-5 with Age and Alzheimer Disease |
| title_full | Association of Plasma Claudin-5 with Age and Alzheimer Disease |
| title_fullStr | Association of Plasma Claudin-5 with Age and Alzheimer Disease |
| title_full_unstemmed | Association of Plasma Claudin-5 with Age and Alzheimer Disease |
| title_short | Association of Plasma Claudin-5 with Age and Alzheimer Disease |
| title_sort | association of plasma claudin 5 with age and alzheimer disease |
| topic | blood–brain barrier claudin-5 tight junction biomarker dementia Alzheimer disease |
| url | https://www.mdpi.com/1422-0067/25/3/1419 |
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