| Intranasal immunotherapy for the treatment of Alzheimer's disease: Escherichia coli LT and LT(R192G) as mucosal adjuvants. | |
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MedLine Citation:
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PMID: 12470794 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Alzheimer's disease (AD) is the most common form of dementia worldwide, yet there is currently no effective treatment or cure. Extracellular deposition of amyloid-beta protein (Abeta) in brain is a key neuropathological characteristic of AD. In 1999, Schenk et al. first reported that an injected Abeta vaccine given to PDAPP mice, an AD mouse model displaying Abeta deposition in brain, led to the lowering of Abeta levels in brain. In 2000, we demonstrated that intranasal (i.n.) immunization with human synthetic Abeta1-40 peptide for 7 months led to a 50-60% reduction in cerebral Abeta burden in PDAPP mice; serum Abeta antibody titers were low (approximately 26 microg/ml). More recently, we have optimized our i.n. Abeta immunization protocol in wild-type (WT) mice. When low doses Escherichia coli heat-labile enterotoxin (LT) were given as a mucosal adjuvant with Abeta i.n., there was a dramatic 12-fold increase in Abeta antibody titers in WT B6D2F1 mice treated two times per week for 8 weeks compared to those of mice receiving i.n. Abeta without adjuvant. A non-toxic form of LT, designated LT(R192G), showed even better adjuvanticity; anti-Abeta antibody titers were 16-fold higher than those seen in mice given i.n. Abeta without adjuvant. In both cases, the serum Abeta antibodies recognized epitopes within Abeta1-15 and were of the immunoglobulin (Ig) isotypes IgG2b, IgG1, IgG2a and low levels of IgA. This new and improved Abeta vaccine protocol is now being tested in AD mouse models with the expectation that higher Abeta antibody titers may be more effective in reducing cerebral Abeta levels. |
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Authors:
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Cynthia A Lemere; Edward T Spooner; Jodi F Leverone; Chica Mori; John D Clements |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Neurobiology of aging Volume: 23 ISSN: 0197-4580 ISO Abbreviation: Neurobiol. Aging Publication Date: 2002 Nov-Dec |
Date Detail:
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Created Date: 2002-12-09 Completed Date: 2003-03-20 Revised Date: 2008-08-20 |
Medline Journal Info:
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Nlm Unique ID: 8100437 Medline TA: Neurobiol Aging Country: United States |
Other Details:
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Languages: eng Pagination: 991-1000 Citation Subset: IM |
Affiliation:
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Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. lemere@cnd.bwh.harvard.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adjuvants, Immunologic
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administration & dosage* Administration, Intranasal Alzheimer Disease / immunology, prevention & control* Alzheimer Vaccines / administration & dosage* Amyloid beta-Protein / immunology* Animals Antibody Formation / drug effects Bacterial Toxins / administration & dosage*, immunology Brain / drug effects, immunology, metabolism, pathology Cell Line Enterotoxins / administration & dosage*, immunology Escherichia coli / immunology* Escherichia coli Proteins* Immunotherapy / methods Male Mice Nasal Mucosa / immunology, metabolism Reference Values Sensitivity and Specificity Species Specificity |
| Chemical | |
Reg. No./Substance:
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0/Adjuvants, Immunologic; 0/Alzheimer Vaccines; 0/Amyloid beta-Protein; 0/Bacterial Toxins; 0/Enterotoxins; 0/Escherichia coli Proteins; 0/heat-labile enterotoxin, E coli |
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