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Molecules of senesc...
Molecules of senescent glial cells differentiate Alzheimer's disease from ageing
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Dai, L. B. (author)
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Gao, F. (author)
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Wang, Q. (author)
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Lv, X. Y. (author)
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Cheng, Z. Z. (author)
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Wu, Y. (author)
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Chai, X. L. (author)
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Levey, A. I. (author)
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Shi, J. (author)
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Shen, Y. (author)
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Journal of Neurology Neurosurgery and Psychiatry. - 0022-3050. ; 94:7, s. 550-9
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Abstract
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- Background Ageing is a major risk factor for Alzheimer's disease (AD), which is accompanied by cellular senescence and thousands of transcriptional changes in the brain. Objectives To identify the biomarkers in the cerebrospinal fluid (CSF) that could help differentiate healthy ageing from neurodegenerative processes. Methods Cellular senescence and ageing-related biomarkers were assessed in primary astrocytes and postmortem brains by immunoblotting and immunohistochemistry. The biomarkers were measured in CSF samples from the China Ageing and Neurodegenerative Disorder Initiative cohort using Elisa and the multiplex Luminex platform. Results The cyclin-dependent kinase inhibitors p16/ p21-positive senescent cells in human postmortem brains were predominantly astrocytes and oligodendrocyte lineage cells, which accumulated in AD brains. CCL2, YKL-40, HGF, MIF, S100B, TSP2, LCN2 and serpinA3 are biomarkers closely related to human glial senescence. Moreover, we discovered that most of these molecules, which were upregulated in senescent glial cells, were significantly elevated in the AD brain. Notably, CSF YKL-40 (beta=0.5412, p<0.0001) levels were markedly elevated with age in healthy older individuals, whereas HGF (beta=0.2732, p=0.0001), MIF (beta=0.33714, p=0.0017) and TSP2 (beta=0.1996, p=0.0297) levels were more susceptible to age in older individuals with AD pathology. We revealed that YKL-40, TSP2 and serpinA3 were useful biomarkers for discriminating patients with AD from CN individuals and non-AD patients. Discussion Our findings demonstrated the different patterns of CSF biomarkers related to senescent glial cells between normal ageing and AD, implicating these biomarkers could identify the road node in healthy path off to neurodegeneration and improve the accuracy of clinical AD diagnosis, which would help promote healthy ageing.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- alzheimer's disease
- neuropathology
- reactive astrocytes
- brain
- alpha-1-antichymotrypsin
- expression
- biomarkers
- dementia
- protein
- association
- correlate
- ykl-40
- Neurosciences & Neurology
- Psychiatry
- Surgery
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Dai, L. B.
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Gao, F.
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Wang, Q.
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Lv, X. Y.
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Cheng, Z. Z.
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Wu, Y.
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show more...
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Chai, X. L.
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Zetterberg, Henr ...
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Blennow, Kaj, 19 ...
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Levey, A. I.
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Shi, J.
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Shen, Y.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Journal of Neuro ...
- By the university
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University of Gothenburg