For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
3
views
57
references
 Top references
cited by
18
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      3,249
      similar
       All similar
      • Record: found
      • Abstract: not found
      • Article: not found

      Immunotherapy for Alzheimer's disease

      Author(s): , , , ,
      Publication date Created:
      Publication date (Electronic):
      Journal: Proceedings of the National Academy of Sciences
      Publisher: Proceedings of the National Academy of Sciences

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The utility of vaccine strategies to treat neurodegenerative diseases such as Alzheimer's disease (AD) may still hold promise. Both active and passive immunization strategies reduced AD-like pathology and restored cognitive deficits in transgenic mice. These results were initially met with considerable optimism; however, phase IIa clinical trials were halted because of a small but significant occurrence of meningoencephalitis. Knowledge gained from studies on amyloid-beta peptide (A beta) immunotherapy will allow optimization of new-generation vaccines, targeting highly specific epitopes while reducing undesired side effects. In harnessing and steering the immune system, an effective response can be generated against A beta. If this proves successful, A beta vaccination could provide the first definitive treatment for AD.

          Related collections

          Most cited references57

          • Record: found
          • Abstract: found
          • Article: not found

          Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis.

          Rakez Kayed, Elizabeth Head, Jennifer L Thompson … (2003)
          Soluble oligomers are common to most amyloids and may represent the primary toxic species of amyloids, like the Abeta peptide in Alzheimer's disease (AD). Here we show that all of the soluble oligomers tested display a common conformation-dependent structure that is unique to soluble oligomers regardless of sequence. The in vitro toxicity of soluble oligomers is inhibited by oligomer-specific antibody. Soluble oligomers have a unique distribution in human AD brain that is distinct from fibrillar amyloid. These results indicate that different types of soluble amyloid oligomers have a common structure and suggest they share a common mechanism of toxicity.
          Article 0 comments Cited 857 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse.

            Dale Schenk, Robin Barbour, Whitney Dunn … (1999)
            Amyloid-beta peptide (Abeta) seems to have a central role in the neuropathology of Alzheimer's disease (AD). Familial forms of the disease have been linked to mutations in the amyloid precursor protein (APP) and the presenilin genes. Disease-linked mutations in these genes result in increased production of the 42-amino-acid form of the peptide (Abeta42), which is the predominant form found in the amyloid plaques of Alzheimer's disease. The PDAPP transgenic mouse, which overexpresses mutant human APP (in which the amino acid at position 717 is phenylalanine instead of the normal valine), progressively develops many of the neuropathological hallmarks of Alzheimer's disease in an age- and brain-region-dependent manner. In the present study, transgenic animals were immunized with Abeta42, either before the onset of AD-type neuropathologies (at 6 weeks of age) or at an older age (11 months), when amyloid-beta deposition and several of the subsequent neuropathological changes were well established. We report that immunization of the young animals essentially prevented the development of beta-amyloid-plaque formation, neuritic dystrophy and astrogliosis. Treatment of the older animals also markedly reduced the extent and progression of these AD-like neuropathologies. Our results raise the possibility that immunization with amyloid-beta may be effective in preventing and treating Alzheimer's disease.
            Article 0 comments Cited 500 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report.

              Roy O Weller, David Wilkinson, James A R Nicoll … (2003)
              Amyloid-beta peptide (Abeta) has a key role in the pathogenesis of Alzheimer disease (AD). Immunization with Abeta in a transgenic mouse model of AD reduces both age-related accumulation of Abeta in the brain and associated cognitive impairment. Here we present the first analysis of human neuropathology after immunization with Abeta (AN-1792). Comparison with unimmunized cases of AD (n = 7) revealed the following unusual features in the immunized case, despite diagnostic neuropathological features of AD: (i) there were extensive areas of neocortex with very few Abeta plaques; (ii) those areas of cortex that were devoid of Abeta plaques contained densities of tangles, neuropil threads and cerebral amyloid angiopathy (CAA) similar to unimmunized AD, but lacked plaque-associated dystrophic neurites and astrocyte clusters; (iii) in some regions devoid of plaques, Abeta-immunoreactivity was associated with microglia; (iv) T-lymphocyte meningoencephalitis was present; and (v) cerebral white matter showed infiltration by macrophages. Findings (i)-(iii) strongly resemble the changes seen after Abeta immunotherapy in mouse models of AD and suggest that the immune response generated against the peptide elicited clearance of Abeta plaques in this patient. The T-lymphocyte meningoencephalitis is likely to correspond to the side effect seen in some other patients who received AN-1792 (refs. 7-9).
              Article 0 comments Cited 256 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Title: Proceedings of the National Academy of Sciences
                Abbreviated Title: Proceedings of the National Academy of Sciences
                Publisher: Proceedings of the National Academy of Sciences
                ISSN (Print): 0027-8424
                ISSN (Electronic): 1091-6490
                Publication date Created: October 05 2004
                Publication date Created: October 05 2004
                Publication date (Electronic): August 05 2004
                Publication date (Print): October 05 2004
                Volume: 101
                Issue: Supplement 2
                Pages: 14657-14662
                Article
                DOI: 10.1073/pnas.0404866101
                PMC ID: 521991
                PubMed ID: 15297619
                SO-VID: 3f1905d3-e8e6-4090-8b44-98bb679b1a95
                Copyright © © 2004
                History

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content3,249

                See all similar

                Cited by17

                See all cited by

                Most referenced authors1,433

                See all reference authors