ArticleProceedings of the National Academy of Sciences of the United States of America2009
Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 197 citations in OpenAlex.
- Blood and Cerebrospinal Fluid Autoantibody to Aβ Levels in Patients with Alzheimer's Disease: a Meta-Analysis Study.Journal of molecular neuroscience : MN · 2020Pooled it
- Safety, tolerability and immunogenicity of vaccine ALZ-101 in patients with early Alzheimer's disease: randomised, controlled trial.Alzheimer's research & therapy · 2026Trial
- B1 Cells for Life.Immunological reviews · 2026Review
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- Plasma Autoantibodies Against Neurodegeneration-Related Antigens in Dementia and Elevated Chi3Li Autoantibodies in Mild Cognitive Impairment.Biomolecules · 2026Article
- Asparaginase-like protein 1 and human endogenous retroviruses link immune and gene dysregulation in dementia.Frontiers in cellular and infection microbiology · 2026Article
- Do human B-1 lymphocytes truly exist?Frontiers in immunology · 2026Review
- Aggregation-Dependent Epitope Sequence and Modification Fingerprints of Anti-Aβ Antibodies.bioRxiv : the preprint server for biology · 2025Article
- Immunosenescence: signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Humoral determinants of checkpoint immunotherapy.Nature · 2025Article
- The role of autoantibodies in Alzheimer's disease: Pathogenetic connections or epiphenomena?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Innate and adaptive immunity in neurodegenerative disease.Cellular and molecular life sciences : CMLS · 2025Review
- Artificial intelligence and omics-based autoantibody profiling in dementia.Frontiers in immunology · 2025Article
- Memory Phenotype Tfh Cells Develop Without Overt Infection and Support Germinal Center Formation and B Cell Responses to Viral Infection.European journal of immunology · 2025Article
- The role of autoantibodies in bridging obesity, aging, and immunosenescence.Immunity & ageing : I & A · 2024Review
- The Emerging Role of Immunoglobulins and Complement in the Stimulation of Neuronal Activity and Repair: Not as Simple as We Thought.Biomolecules · 2024Review
- Review
- The immunology of B-1 cells: from development to aging.Immunity & ageing : I & A · 2024Review
- Comparative methods for quantifying plasma biomarkers in Alzheimer's disease: Implications for the next frontier in cerebral amyloid angiopathy diagnostics.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Autoantibodies to Interferons in Infectious Diseases.Viruses · 2023Review
46 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 12 institutions in 3 countries.
Funding
Abstract
A number of distinct beta-amyloid (Abeta) variants or multimers have been implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides are in clinical trials. Humans have natural Abeta-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 Abeta and amyloidogenic non-Abeta 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 Abeta and pyroglutamate or oxidized residues, and IgGs specific for oligomeric preparations of Abeta1-42 in particular declined with age and advancing AD. Most individuals showed unexpected antibody reactivities against peptides unique to autosomal dominant forms of dementia (mutant Abeta, ABri, ADan) and IgGs isolated from plasma of AD patients or healthy controls protected primary neurons from Abeta toxicity. Aged vervets showed similar patterns of plasma IgG antibodies against amyloid peptides, and after immunization with Abeta the monkeys developed high titers not only against Abeta 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 Abeta 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.