The DOI matches its Crossref record; 64 of the 65 references it cites were found in a registry or an index.
Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease
Open accessAbstract
A number of distinct β-amyloid (Aβ) variants or multimers have been implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides are in clinical trials. Humans have natural Aβ-specific antibodies, but their diversity, abundance, and function in the general population remain largely unknown. Here, we demonstrate with peptide microarrays the presence of natural antibodies against known toxic Aβ and amyloidogenic non-Aβ species in plasma samples and cerebrospinal fluid of AD patients and healthy controls aged 21–89 years. Antibody reactivity was most prominent against oligomeric assemblies of Aβ and pyroglutamate or oxidized residues, and IgGs specific for oligomeric preparations of Aβ1-42 in particular declined with age and advancing AD. Most individuals showed unexpected antibody reactivities against peptides unique to autosomal dominant forms of dementia (mutant Aβ, ABri, ADan) and IgGs isolated from plasma of AD patients or healthy controls protected primary neurons from Aβ toxicity. Aged vervets showed similar patterns of plasma IgG antibodies against amyloid peptides, and after immunization with Aβ the monkeys developed high titers not only against Aβ peptides but also against ABri and ADan peptides. Our findings support the concept of conformation-specific, cross-reactive antibodies that may protect against amyloidogenic toxic peptides. If a therapeutic benefit of Aβ antibodies can be confirmed in AD patients, stimulating the production of such neuroprotective antibodies or passively administering them to the elderly population may provide a preventive measure toward AD.
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“their level inversely correlate with the number of amyloid plaques [97,98].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [97]
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“These antibodies to toxic forms of A β are present in the plasma and CSF of patients and healthy controls”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [97]
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1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
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Self-citationBohrmann, B., Baumann, K., Benz, J., Gerber, F., Huber, W., Knoflach, F., Messer, J., Oroszlan, K., Rauchenberger, R., Richter, W. F., et al. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-110977 · Cited by 448
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Metadata
- Authors
- Britschgi, M., Olin, C. E., Johns, H. T., Takeda-Uchimura, Y., LeMieux, M. C., Rufibach, K., Rajadas, J., Zhang, H., Tomooka, B., Robinson, W. H., Clark, C. M., Fagan, A. M., Galasko, D. R., Holtzman, D. M., Jutel, M., Kaye, J. A., Lemere, C. A., Leszek, J., Li, G., Peskind, E. R., Quinn, J. F., Yesavage, J. A., Ghiso, J. A., & Wyss-Coray, T.
- Affiliations
- Stanford Medicine (US)
- Stanford University (US)
- Departments of aNeurology and Neurological Sciences and
- University of Zurich (CH)
- VA Palo Alto Health Care System (US)
- University of Pennsylvania (US)
- Washington University in St. Louis (US)
- University of California San Diego (US)
- Wroclaw Medical University (PL)
- Oregon Health & Science University (US)
- Brigham and Women's Hospital (US)
- University of Washington (US)
- NYU Langone Health (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-07-21
- Volume
- 106
- Issue
- 29
- Pages
- 12145-12150
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2715538
- OpenAlex
- W2132576841
- Cited by
- 201
- References
- 65
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 8 · 2023: 11 · 2022: 16 · 2021: 9 · 2020: 15 · 2019: 7 · 2018: 5 · 2017: 4 · 2016: 16 · 2015: 12 · 2014: 10 · 2013: 12 · 2012: 20
- FWCI
- 12.41
- 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)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institute on Aging (P01AG010491, AG10491, AG 08017, AG20603, R01AG020603, P30AG008017, R01AG030539, AG030539, P50AG005136)
- National Institute of Neurological Disorders and Stroke (R01NS136122)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
- Alzheimer's disease, natural antibodies, amyloid-beta, amyloid oligomers, neuroprotection, aging, cerebrospinal fluid, plasma IgG, pyroglutamic acid, ABRI, Adán, conformation-specific antibodies, vervet monkey, immunization, passive immunotherapy, peptide microarrays
- MeSH terms
- Aging, Alzheimer Disease, Animals, Antibodies, Dementia, Genes, Dominant, Immunoglobulin G, Immunization, Molecular Weight, Neurons, Peptides, Primates, Protein Processing, Post-Translational, Amyloid beta-Peptides, Disease Progression, Neuroprotective Agents, Cytoprotection, Protein Structure, Quaternary, Mice
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