ArticleProceedings of the National Academy of Sciences of the United States of America2007
Transcutaneous beta-amyloid immunization reduces cerebral beta-amyloid deposits without T cell infiltration and microhemorrhage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 64 citations in OpenAlex.
- Vaccines for Alzheimer's disease: a brief scoping review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Identification of genetic molecular markers and immune infiltration characteristics of Alzheimer's disease through weighted gene co-expression network analysis.Frontiers in neurology · 2022Article
- T Cell-Mediated Autoimmunity in Glaucoma Neurodegeneration.Frontiers in immunology · 2021Review
- Injury intensifies T cell mediated graft-versus-host disease in a humanized model of traumatic brain injury.Scientific reports · 2020Article
- Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer's disease.Journal of neuroinflammation · 2019Review
- T-cell-mediated regulation of neuroinflammation involved in neurodegenerative diseases.Journal of neuroinflammation · 2014Review
- Prominence of central sphingosine-1-phosphate receptor-1 in attenuating aβ-induced injury by fingolimod.Journal of molecular neuroscience : MN · 2014Article
- Vaccination induced changes in pro-inflammatory cytokine levels as an early putative biomarker for cognitive improvement in a transgenic mouse model for Alzheimer disease.Human vaccines & immunotherapeutics · 2014Article
- Innate immunity in Alzheimer's disease: a complex affair.CNS & neurological disorders drug targets · 2013Review
- Article
- Recent rodent models for Alzheimer's disease: clinical implications and basic research.Journal of neural transmission (Vienna, Austria : 1996) · 2012Review
- Association of skin with the pathogenesis and treatment of neurodegenerative amyloidosis.Frontiers in neurology · 2012Article
- The "brain-skin connection" in protein misfolding and amyloid deposits: embryological, pathophysiological, and therapeutic common grounds?Frontiers in neurology · 2012Article
- How to get from here to there: macrophage recruitment in Alzheimer's disease.Current Alzheimer research · 2011Review
- Murine models of Alzheimer's disease and their use in developing immunotherapies.Biochimica et biophysica acta · 2010Review
- Alzheimer disease.Disease-a-month : DM · 2010Review
- Immunization with the SDPM1 peptide lowers amyloid plaque burden and improves cognitive function in the APPswePSEN1(A246E) transgenic mouse model of Alzheimer's disease.Neurobiology of disease · 2010Article
- Amyloid-beta immunotherapy for Alzheimer's disease.CNS & neurological disorders drug targets · 2010Review
- Abeta DNA vaccination for Alzheimer's disease: focus on disease prevention.CNS & neurological disorders drug targets · 2010Review
- Immunotherapeutic approaches for Alzheimer's disease in transgenic mouse models.Brain structure & function · 2010Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Alzheimer's disease (AD) immunotherapy accomplished by vaccination with beta-amyloid (Abeta) peptide has proved efficacious in AD mouse models. However, "active" Abeta vaccination strategies for the treatment of cerebral amyloidosis without concurrent induction of detrimental side effects are lacking. We have developed a transcutaneous (t.c.) Abeta vaccination approach and evaluated efficacy and monitored for deleterious side effects, including meningoencephalitis and microhemorrhage, in WT mice and a transgenic mouse model of AD. We demonstrate that t.c. immunization of WT mice with aggregated Abeta(1-42) plus the adjuvant cholera toxin (CT) results in high-titer Abeta antibodies (mainly of the Ig G1 class) and Abeta(1-42)-specific splenocyte immune responses. Confocal microscopy of the t.c. immunization site revealed Langerhans cells in areas of the skin containing the Abeta(1-42) immunogen, suggesting that these unique innate immune cells participate in Abeta(1-42) antigen processing. To evaluate the efficacy of t.c. immunization in reducing cerebral amyloidosis, transgenic PSAPP (APPsw, PSEN1dE9) mice were immunized with aggregated Abeta(1-42) peptide plus CT. Similar to WT mice, PSAPP mice showed high Abeta antibody titers. Most importantly, t.c. immunization with Abeta(1-42) plus CT resulted in significant decreases in cerebral Abeta(1-40,42) levels coincident with increased circulating levels of Abeta(1-40,42), suggesting brain-to-blood efflux of Abeta. Reduction in cerebral amyloidosis was not associated with deleterious side effects, including brain T cell infiltration or cerebral microhemorrhage. Together, these data suggest that t.c. immunization constitutes an effective and potentially safe treatment strategy for AD.
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