Clusterin promotes amyloid plaque formation and is critical for neuritic toxicity in a mouse model of Alzheimer's disease
Open accessAbstract
Studies have shown that clusterin (also called apolipoprotein J) can influence the structure and toxicity of amyloid-beta (Abeta) in vitro. To determine whether endogenous clusterin plays a role in influencing Abeta deposition, structure, and toxicity in vivo, we bred PDAPP mice, a transgenic mouse model of Alzheimer's disease, to clusterin(-/-) mice. By 12 months of age, PDAPP, clusterin(-/-) mice had similar levels of brain Abeta deposition as did PDAPP, clusterin(+/+) mice. Although Abeta deposition was similar, PDAPP, clusterin(-/-) mice had significantly fewer fibrillar Abeta (amyloid) deposits than PDAPP mice expressing clusterin. In the absence of clusterin, neuritic dystrophy associated with the deposited amyloid was markedly reduced, resulting in a dissociation between fibrillar amyloid formation and neuritic dystrophy. These findings demonstrate that clusterin markedly influences Abeta structure and neuritic toxicity in vivo and is likely to play an important role in Alzheimer's disease pathogenesis.
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ApoJ (clusterin) facilitates fibrillar amyloid plaque formation.
“ApoJ, also known as clusterin, has been shown to facilitate fibrillar amyloid plaque formation (DeMattos et al., 2002).”
From Overexpression of Low-Density Lipoprotein Receptor in the Brain Markedly Inhibits Amyloid Deposition and Increases Extracellular Aβ Clearance (2009) · cites this paper as DeMattos et al., 2002
ApoJ deficiency significantly reduced fibrillar amyloid plaque formation and neuritic toxicity in a mouse model of amyloidosis.
“ApoA-I deficiency did not alter amyloid pathology (Fagan et al., 2004), while apoJ deficiency significantly reduced fibrillar amyloid plaque formation and neuritic toxicity in a mouse model of amyloidosis (DeMattos et al., 2002).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as DeMattos et al., 2002
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- Authors
- DeMattos, R. B., O'dell, M. A., Parsadanian, M., Taylor, J. W., Harmony, J. A. K., Bales, K. R., Paul, S. M., Aronow, B. J., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Center for the Study of Nervous System Injury, Alzheimer's Disease Research Center, and Departments of Neurology and Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8111, St. Louis, MO 63110; Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45627-0575; Division of Molecular and Developmental Biology, Children's Hospital Research Foundation, Cincinnati, OH 45229-3039; Neuroscience...
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-07-26
- Volume
- 99
- Issue
- 16
- Pages
- 10843-10848
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC125060
- OpenAlex
- W2041393510
- Cited by
- 359
- References
- 7
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 20 · 2023: 10 · 2022: 19 · 2021: 13 · 2020: 33 · 2019: 11 · 2018: 15 · 2017: 8 · 2016: 18 · 2015: 10 · 2014: 14 · 2013: 13 · 2012: 16
- FWCI
- 10.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- National Institutes of Health (AG05681, AG13956, AG11355)
- National Institute on Aging (AG11355, R01AG013956, AG 05681, P50AG005681, R37AG013956, AG13956, P01AG011355)
- 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, amyloid-beta, amyloid plaque formation, neuritic dystrophy, Alzheimer's disease, PDAPP mice, amyloid-beta toxicity, transgenic mouse model
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Glycoproteins, Peptide Fragments, Thiazoles, Amyloid beta-Peptides, Neurites, Amyloid beta-Protein Precursor, Mice, Knockout, Molecular Chaperones, Clusterin, Mice, Benzothiazoles, Plaque, Amyloid
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