Human apolipoprotein A–I binds amyloid-β and prevents Aβ-induced neurotoxicity
Abstract
Aggregates of the amyloid-beta peptide (Abeta) play a central role in the pathogenesis of Alzheimer's disease (AD). Identification of proteins that physiologically bind Abeta and modulate its aggregation and neurotoxicity could lead to the development of novel disease-modifying approaches in AD. By screening a phage display peptide library for high affinity ligands of aggregated Abeta(1-42), we isolated a peptide homologous to a highly conserved amino acid sequence present in the N-terminus of apolipoprotein A-I (apoA-I). We show that purified human apoA-I and Abeta form non-covalent complexes and that interaction with apoA-I affects the morphology of amyloid aggregates formed by Abeta. Significantly, Abeta/apoA-I complexes were also detected in cerebrospinal fluid from AD patients. Interestingly, apoA-I and apoA-I-containing reconstituted high density lipoprotein particles protect hippocampal neuronal cultures from Abeta-induced oxidative stress and neurodegeneration. These results suggest that human apoA-I modulates Abeta aggregation and Abeta-induced neuronal damage and that the Abeta-binding domain in apoA-I may constitute a novel framework for the design of inhibitors of Abeta toxicity.
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Both 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 Paula-Lima et al., 2009
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The role of apolipoprotein E in Alzheimer's disease
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- Authors
- Paula-Lima, A. C., Tricerri, M. A., Brito-Moreira, J., Bomfim, T. R., Oliveira, F. F., Magdesian, M. H., Grinberg, L. T., Panizzutti, R., & Ferreira, S. T.
- Affiliations
- Biochemistry Research Institute of La Plata (AR)
- Universidade Federal do Rio de Janeiro (BR)
- Universidade de São Paulo (BR)
- Venue
- The International Journal of Biochemistry & Cell Biology
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 41
- Issue
- 6
- Pages
- 1361-1370
- ISSN
- 1357-2725 (ISSN-L)
- OpenAlex
- W2048756000
- Cited by
- 121
- References
- 7
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 7 · 2023: 5 · 2022: 13 · 2021: 8 · 2020: 12 · 2019: 9 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 4 · 2012: 11
- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The International Journal of Biochemistry & Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Universidade de São Paulo
- 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 › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein A-I, amyloid-beta, Alzheimer's disease, amyloid-beta aggregation, neurotoxicity, peptide ligands, phage display, high-density lipoprotein, oxidative stress, hippocampal neurons, cerebrospinal fluid, neurodegeneration
- MeSH terms
- Alzheimer Disease, Amino Acid Sequence, Animals, Electrophoresis, Polyacrylamide Gel, Female, Humans, Neurons, Peptide Fragments, Pregnancy, Amyloid beta-Peptides, Apolipoprotein A-I, Rats, Sprague-Dawley, Oxidative Stress, Rats
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