Amyloid-beta uptake by blood monocytes is reduced with ageing and Alzheimer’s disease

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Abstract

Deficits in the clearance of amyloid β-protein (Aβ) play a pivotal role in the pathogenesis of sporadic Alzheimer’s disease (AD). The roles of blood monocytes in the development of AD remain unclear. In this study, we sought to investigate the alterations in the Aβ phagocytosis function of peripheral monocytes during ageing and in AD patients. A total of 104 cognitively normal participants aged 22–89 years, 24 AD patients, 25 age- and sex-matched cognitively normal (CN) subjects, 15 Parkinson’s disease patients (PD), and 15 age- and sex-matched CN subjects were recruited. The Aβ uptake by blood monocytes was measured and its alteration during ageing and in AD patients were investigated. Aβ _1-42 uptake by monocytes decreased during ageing and further decreased in AD but not in PD patients. Aβ _1-42 uptake by monocytes was associated with Aβ _1-42 levels in the blood. Among the Aβ uptake-related receptors and enzymes, the expression of Toll-like receptor 2 (TLR2) was reduced in monocytes from AD patients. Our findings suggest that monocytes regulate the blood levels of Aβ and might be involved in the development of AD. The recovery of the Aβ uptake function by blood monocytes represents a potential therapeutic strategy for AD.

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Author and article information

Contributors

Yang Chen:

ORCID: http://orcid.org/0000-0003-3117-7231

cytgzy2020@163.com

Yan-Jiang Wang:

ORCID: http://orcid.org/0000-0002-6227-6112

yanjiang_wang@tmmu.edu.cn

Journal

Journal ID (nlm-ta): Transl Psychiatry

Journal ID (iso-abbrev): Transl Psychiatry

Title: Translational Psychiatry

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2158-3188

Publication date (Electronic): 8 December 2020

Publication date PMC-release: 8 December 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 423

Affiliations

[1 ]GRID grid.410570.7, ISNI 0000 0004 1760 6682, Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, , Third Military Medical University, ; Chongqing, China

[2 ]GRID grid.410570.7, ISNI 0000 0004 1760 6682, The Institute of Brain and Intelligence, , Third Military Medical University, ; Chongqing, China

[3 ]Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, China

[4 ]GRID grid.410570.7, ISNI 0000 0004 1760 6682, Department of Health Management, Daping Hospital, , Third Military Medical University, ; Chongqing, China

[5 ]GRID grid.410570.7, ISNI 0000 0004 1760 6682, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, , Third Military Medical University, ; Chongqing, China

[6 ]GRID grid.9227.e, ISNI 0000000119573309, Center for Excellence in Brain Science and Intelligence Technology, , Chinese Academy of Sciences, ; Shanghai, China

Author information

Ying-Ying Shen http://orcid.org/0000-0002-5711-9251

Yuan Cheng http://orcid.org/0000-0002-1707-8184

Xian-Le Bu http://orcid.org/0000-0002-2331-3339

Fan Zeng http://orcid.org/0000-0003-4559-292X

Zhi-Qiang Xu http://orcid.org/0000-0002-5536-3293

Yang Chen http://orcid.org/0000-0003-3117-7231

Yan-Jiang Wang http://orcid.org/0000-0002-6227-6112

Article

Publisher ID: 1113

DOI: 10.1038/s41398-020-01113-9

PMC ID: 7722845

PubMed ID: 33293506

SO-VID: ee58ccbb-0ace-4ef1-bee0-a44f45577363

License:

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