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Review
. 2008 Sep;7(9):805-11.
doi: 10.1016/S1474-4422(08)70170-4. Epub 2008 Jul 28.

Amyloid-beta immunisation for Alzheimer's disease

Affiliations
Review

Amyloid-beta immunisation for Alzheimer's disease

Thomas Wisniewski et al. Lancet Neurol. 2008 Sep.

Abstract

Alzheimer's disease is the main cause of dementia in elderly people and is becoming an ever greater problem as societies worldwide age. Treatments that stop or at least effectively modify disease course do not yet exist. In Alzheimer's disease, the conversion of the amyloid-beta peptide (Abeta) from a physiological water-soluble monomeric form into neurotoxic oligomeric and fibrillar forms rich in stable beta-sheet conformations is an important event. The most toxic forms of Abeta are thought to be oligomers, and dimers might be the smallest neurotoxic species. Numerous immunological approaches that prevent the conversion of the normal precursor protein into pathological forms or that accelerate clearance are in development. More than ten new approaches to active and passive immunotherapy are under investigation in clinical trials with the aim of producing safe methods for immunological therapy and prevention. A delicate balance between immunological clearance of an endogenous protein with acquired toxic properties and the induction of an autoimmune reaction must be found.

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Conflict of interest statement

Conflicts of interest

TW has no conflicts of interest. UK is co-author on a patent for the tissue amyloid plaque immunoreactivity (TAPIR) assay, held by the University of Zurich.

Figures

Figure 1
Figure 1. Potential mechanisms of immunomodulation for amyloid-β related pathology
Direct disassembly of plaques by conformation-selective antibodies (1); antibody mediated activation of microglial cells (2); non-Fc mediated activation of microglia (3); creation of periferal sink by clearance of circulating amyloid β (4); IgM-mediated hydrolysis (5); neutralisation of oligomer toxicity (6). These mechanisms are not mutually exclusive. More than one mechanism could play a part at any give time, with different mechanisms potentially having a role at different stages of disease.

References

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