Trajectory of changes in myelin basic protein levels in cerebrospinal fluid during ageing and its association with biomarkers of Alzheimer’s disease

Abstract Myelin loss has been implicated in the development of Alzheimer’s disease (AD). We investigated the changes in myelin basic protein (MBP) levels in cerebrospinal fluid (CSF) in an ageing cohort comprising 116 cognitively normal and Aβ-negative controls aged 26 to 82 years, as well as in a c...

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Main Authors: Man-Yu Xu, Xu Yi, Shan Huang, Qing-Hua Wang, Yu-Jie Lai, Zhen Wang, Dong-Yu Fan, Gui-Hua Zeng, Yu-Di Bai, Ying-Ying Shen, Fan Zeng, Qing-Xiang Mao, Zhi-Qiang Xu, Feng Mei, Yan-Jiang Wang, Jun Wang
Format: Article
Language:English
Published: Nature Publishing Group 2025-04-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-025-03369-5
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author Man-Yu Xu
Xu Yi
Shan Huang
Qing-Hua Wang
Yu-Jie Lai
Zhen Wang
Dong-Yu Fan
Gui-Hua Zeng
Yu-Di Bai
Ying-Ying Shen
Fan Zeng
Qing-Xiang Mao
Zhi-Qiang Xu
Feng Mei
Yan-Jiang Wang
Jun Wang
author_facet Man-Yu Xu
Xu Yi
Shan Huang
Qing-Hua Wang
Yu-Jie Lai
Zhen Wang
Dong-Yu Fan
Gui-Hua Zeng
Yu-Di Bai
Ying-Ying Shen
Fan Zeng
Qing-Xiang Mao
Zhi-Qiang Xu
Feng Mei
Yan-Jiang Wang
Jun Wang
author_sort Man-Yu Xu
collection DOAJ
description Abstract Myelin loss has been implicated in the development of Alzheimer’s disease (AD). We investigated the changes in myelin basic protein (MBP) levels in cerebrospinal fluid (CSF) in an ageing cohort comprising 116 cognitively normal and Aβ-negative controls aged 26 to 82 years, as well as in a clinical cohort. We found that CSF MBP levels was positively correlated with age in a nonlinear pattern over the lifetime of the ageing cohort and that CSF MBP continually increased until it began to decline around age of 51 years and rose again around age 62. CSF MBP levels were correlated with the Mini-Mental State Examination (MMSE) score and CSF phosphorylated tau-181 (p-tau181) and total tau (t-tau) levels but not the Aβ42/Aβ40 ratio. CSF MBP levels moderated age-related changes in cognitive function. In the clinical cohort, CSF MBP levels were higher in the CSF Aβ+ patients than in the CSF Aβ- participants, and CSF MBP levels were higher in the Aβ–PET+ patients than in the Aβ–PET- participants. CSF MBP levels were higher in apolipoprotein E ε4 allele (APOE-ε4) carriers than in APOE-ε4 noncarriers in the clinical cohort. Our study reveals the possible changes in CSF MBP levels during ageing and in AD patients, providing evidence that demyelination is involved in brain ageing and AD pathogenesis in humans.
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spelling doaj-art-a69bdab75dd0417bb57922eb0a766a7f2025-08-20T03:18:28ZengNature Publishing GroupTranslational Psychiatry2158-31882025-04-011511810.1038/s41398-025-03369-5Trajectory of changes in myelin basic protein levels in cerebrospinal fluid during ageing and its association with biomarkers of Alzheimer’s diseaseMan-Yu Xu0Xu Yi1Shan Huang2Qing-Hua Wang3Yu-Jie Lai4Zhen Wang5Dong-Yu Fan6Gui-Hua Zeng7Yu-Di Bai8Ying-Ying Shen9Fan Zeng10Qing-Xiang Mao11Zhi-Qiang Xu12Feng Mei13Yan-Jiang Wang14Jun Wang15Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of ICU, Daping Hospital, Third Military Medical UniversityDepartment of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of Anesthesiology, Daping Hospital, Third Military Medical UniversityDepartment of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of Histology and Embryology, Third Military Medical UniversityDepartment of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityDepartment of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical UniversityAbstract Myelin loss has been implicated in the development of Alzheimer’s disease (AD). We investigated the changes in myelin basic protein (MBP) levels in cerebrospinal fluid (CSF) in an ageing cohort comprising 116 cognitively normal and Aβ-negative controls aged 26 to 82 years, as well as in a clinical cohort. We found that CSF MBP levels was positively correlated with age in a nonlinear pattern over the lifetime of the ageing cohort and that CSF MBP continually increased until it began to decline around age of 51 years and rose again around age 62. CSF MBP levels were correlated with the Mini-Mental State Examination (MMSE) score and CSF phosphorylated tau-181 (p-tau181) and total tau (t-tau) levels but not the Aβ42/Aβ40 ratio. CSF MBP levels moderated age-related changes in cognitive function. In the clinical cohort, CSF MBP levels were higher in the CSF Aβ+ patients than in the CSF Aβ- participants, and CSF MBP levels were higher in the Aβ–PET+ patients than in the Aβ–PET- participants. CSF MBP levels were higher in apolipoprotein E ε4 allele (APOE-ε4) carriers than in APOE-ε4 noncarriers in the clinical cohort. Our study reveals the possible changes in CSF MBP levels during ageing and in AD patients, providing evidence that demyelination is involved in brain ageing and AD pathogenesis in humans.https://doi.org/10.1038/s41398-025-03369-5
spellingShingle Man-Yu Xu
Xu Yi
Shan Huang
Qing-Hua Wang
Yu-Jie Lai
Zhen Wang
Dong-Yu Fan
Gui-Hua Zeng
Yu-Di Bai
Ying-Ying Shen
Fan Zeng
Qing-Xiang Mao
Zhi-Qiang Xu
Feng Mei
Yan-Jiang Wang
Jun Wang
Trajectory of changes in myelin basic protein levels in cerebrospinal fluid during ageing and its association with biomarkers of Alzheimer’s disease
Translational Psychiatry
title Trajectory of changes in myelin basic protein levels in cerebrospinal fluid during ageing and its association with biomarkers of Alzheimer’s disease
title_full Trajectory of changes in myelin basic protein levels in cerebrospinal fluid during ageing and its association with biomarkers of Alzheimer’s disease
title_fullStr Trajectory of changes in myelin basic protein levels in cerebrospinal fluid during ageing and its association with biomarkers of Alzheimer’s disease
title_full_unstemmed Trajectory of changes in myelin basic protein levels in cerebrospinal fluid during ageing and its association with biomarkers of Alzheimer’s disease
title_short Trajectory of changes in myelin basic protein levels in cerebrospinal fluid during ageing and its association with biomarkers of Alzheimer’s disease
title_sort trajectory of changes in myelin basic protein levels in cerebrospinal fluid during ageing and its association with biomarkers of alzheimer s disease
url https://doi.org/10.1038/s41398-025-03369-5
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