Possible neuroprotective role of clusterin in Alzheimer's disease: a quantitative immunocytochemical study
Abstract
Clusterin is a secreted glycoprotein that is expressed in response to tissue injury both in peripheral organs and in the brain. Recent studies have shown a substantial increase in clusterin mRNA in pyramidal neurons of the hippocampus and the entorhinal cortex in Alzheimer's disease (AD), with clusterin immunoreactivity occurring in neuropil threads, neurofibrillary tangles (NFT), and senile plaques. To elucidate further the role of this protein in the degenerative process, a quantitative study of its distribution in the cerebral cortex of non-demented and AD patients, all older than 85 years of age, was performed using immunocytochemistry. Using a stereological approach, we found that in cortical areas affected in AD, such as the entorhinal, inferior temporal and superior frontal cortices, the percentage of NFT-free neurons displaying clusterin immunoreactivity was significantly higher than that in non-demented cases. No such increase in the density of clusterin-immunoreactive neurons was seen in cortical areas that were less affected in the disease process. Furthermore, clusterin immunoreactivity was rarely observed in NFT-containing neurons. In conjunction with previous observations in peripheral tissues, these data suggest that clusterin may have a neuroprotective role, and that in AD, low cellular expression of this protein may be associated with neuronal degeneration and death.
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In Alzheimer's disease brain, CLU expression is increased in affected cortical areas and is present in amyloid plaques and cerebrospinal fluid of AD cases.
“In Alzheimer's disease brain, CLU expression is reported to be increased in affected cortical areas and is present in amyloid plaques and in the cerebrospinal fluid of AD cases [17][18][19][20] .”
From Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease (2009) · cites this paper as [19]
Cites
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“Neuron densities per mm3 were evaluated using the optical disector, an stereological counting method which ensures that all regions within the structure of interest have an equal chance of being analyzed, and that counts do not depend on the size and shape of neurons [25, 56, 61, 62].”
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“Neuron densities per mm3 were evaluated using the optical disector, an stereological counting method which ensures that all regions within the structure of interest have an equal chance of being analyzed, and that counts do not depend on the size and shape of neurons [25, 56, 61, 62].”
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Distribution of clusterin in Alzheimer brain tissue
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Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326 · see citing works
Clusterin in Alzheimer’s Disease: Mechanisms, Genetics, and Lessons From Other Pathologies
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Sustained astrocytic clusterin expression improves remodeling after brain ischemia
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- Authors
- Giannakopoulos, P., Kövari, E., French, L. E., Viard, I., Hof, P. R., & Bouras, C.
- Affiliations
- University of Geneva (CH)
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- Acta Neuropathologica
- Published
- 1998-04-16
- Volume
- 95
- Issue
- 4
- Pages
- 387-394
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2024910613
- Cited by
- 90
- References
- 5
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 4 · 2013: 4 · 2012: 6
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institutes of Health
- National Institute on Aging (AG 05138, P50AG005138)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Clusterin in disease pathology
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- clusterin, Alzheimer's disease, neuroprotection, neurofibrillary tangles, amyloid plaques, cerebral cortex, entorhinal cortex, inferior temporal cortex, superior frontal cortex, neurodegeneration, stereology, immunoreactive neurons
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Antibodies, Monoclonal, Brain, Brain Chemistry, Cerebral Cortex, Female, Glycoproteins, Humans, Immunohistochemistry, Male, Nerve Tissue Proteins, Neurofibrillary Tangles, tau Proteins, Molecular Chaperones, Clusterin
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