The cerebrospinal-fluid soluble form of Alzheimer's amyloid β is complexed to SP-40,40 (apolipoprotein J), an inhibitor of the complement membrane-attack complex
Open accessAbstract
The amyloid fibrils deposited in Alzheimer's neuritic plaque cores and cerebral blood vessels are mainly composed of aggregated forms of a unique peptide, 39-42 amino acids long, named amyloid beta (A beta). A similar, although soluble, A beta (‘sA beta’) has been identified in cerebrospinal fluid, plasma and cell supernatants, indicating that it is normally produced by proteolytic processing of its precursor protein, amyloid precursor protein (APP). Using direct binding experiments we have isolated and characterized an 80 kDa circulating protein that specifically interacts with a synthetic peptide identical with A beta. The protein was unmistakably identified as SP-40,40 or ApoJ, a cytolytic inhibitor and lipid carrier, by means of amino acid sequence and immunoreactivity with specific antibodies. Immunoprecipitation with anti-SP-40,40 retrieved soluble A beta from cerebrospinal fluid, indicating that the interaction occurs in vivo.
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Clusterin interacts with soluble Aβ and forms complexes that cross the blood-brain barrier.
“It interacts with the soluble form of Aβ in animal models of disease and binds soluble Aβ in a specific and reversible manner, forming complexes that have been shown to cross the blood-brain barrier [21][22][23][24] .”
From Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease (2009) · cites this paper as [22]
The Results and Discussion report that SP-40,40 (clusterin/ApoJ) specifically binds Aβ in vitro and in vivo, supporting the interaction. The same section describes transport of soluble Aβ through the blood–brain barrier only as a potential mechanism; it does not show that the complexes cross it. The cited passages also concern human samples, not animal disease models. (LLM, conf=0.88)
Experimental — accuracy not yet measuredBoth apoA-I and apoJ bind to Aβ and prevent Aβ aggregation and toxicity in vitro.
“Both apoA-I and apoJ are known to bind to Aβ and prevent Aβ aggregation and toxicity in vitro (Ghiso et al., 1993; Koldamova et al., 2001; Paula-Lima et al., 2009).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Ghiso et al., 1993
The Introduction and Results and Discussion report that apoJ binds Aβ in vitro and is associated with soluble Aβ in cerebrospinal fluid. The Introduction explicitly says the authors tested only the binding part of their hypothesis that this interaction might prevent aggregation. Our copy does not establish that apoJ prevents Aβ aggregation or toxicity, and it does not address apoA-I. (LLM, conf=0.90)
Experimental — accuracy not yet measuredClusterin binds soluble amyloid-beta with high affinity and associates specifically with amyloid-beta 40.
“CLU has high affinity for soluble Aβ (Ghiso, et al., 1993) and associates specifically with Aβ40 (Howlett, et al., 2013)”
From A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin (2016) · cites this paper as Ghiso, et al., 1993
Clusterin is secreted by astrocytes, complexes with soluble Aβ, is present in plaques, and directly activates microglia.
“Clusterin, which is secreted by astrocytes, has been found to complex to soluble Aβ [35], is present in plaques [36–38], and directly activates microglia [39].”
From Microglial dysfunction in brain aging and Alzheimer's disease (2014) · cites this paper as [35]
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References 53 · Cited by 304
Research works printed but not linked: 7
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- Authors
- Ghiso, J., Matsubara, E., Koudinov, A., Choi-Miura, N. H., Tomita, M., Wisniewski, T., & Frangione, B.
- Affiliations
- NYU Langone Health (US)
- SHOWA Medical University (JP)
- Department of Neurology, New York University Medical Center, 550 First Avenue, New York, NY 10016, U.S.A.
- ORCID
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1993-07-01
- Volume
- 293
- Issue
- 1
- Pages
- 27-30
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1134315
- OpenAlex
- W1821582401
- Cited by
- 304
- References
- 53
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 5 · 2022: 9 · 2021: 6 · 2020: 14 · 2019: 6 · 2018: 6 · 2017: 8 · 2016: 11 · 2015: 8 · 2014: 6 · 2013: 10 · 2012: 13
- FWCI
- 10.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r35ag010953-07)
- National Institute on Aging (R01AG008721, AG-08721, AG10953, AG05891)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Keywords
- amyloid-beta, soluble amyloid-beta, clusterin, cerebrospinal fluid, protein-peptide interactions, membrane attack complex, amyloid precursor protein, Alzheimer's disease, neuritic plaques
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Chromatography, Affinity, Electrophoresis, Polyacrylamide Gel, Glycoproteins, Humans, Molecular Sequence Data, Solubility, Immunoblotting, Complement Membrane Attack Complex, Amyloid beta-Peptides, Molecular Chaperones, Clusterin
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