Aβ immunization and anti-Aβ antibodies: Potential therapies for the prevention and treatment of Alzheimer's disease

David M. Holtzman, Kelly R. Bales, Steven M. Paul, Ronald B. DeMattos

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Amyloid-β (Aβ) is a normally soluble 39-43 amino peptide. Genetic and biochemical data strongly suggest that the conversion of Aβ from soluble to insoluble forms with high β-sheet content and its buildup in the brain is a key step in the pathogenesis of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). Prevention and/or reversal of this process may serve as a treatment. Methods to prevent or reverse Aβ deposition and its toxic effects would include decreasing its production, preventing its conversion to insoluble forms (e.g. inhibit β-sheet formation) or in changing the dynamics of extracellular brain Aβ, either locally within the brain or by altering net flux of Aβ between the central nervous system (CNS) and plasma compartment. Transgenic mouse models of AD that develop age-dependent Aβ deposition, damage to the neuropil, and behavioral deficits have enabled researchers to test whether different manipulations can influence these AD-like changes. Recently, active immunization with different forms of the Aβ peptide has been shown to decrease brain Aβ deposition and improve cognitive performance in mouse models of AD. Certain peripherally administered anti-Aβ antibodies have similar effects. The mechanism(s) by which anti-Aβ antibodies result in these effects is just beginning to be elucidated. Aβ-related immune therapies in humans are an exciting new area of AD research. Understanding their detailed mechanism(s) of action and their potential usefulness awaits the results of future animal and human studies.

Original languageEnglish
Pages (from-to)1603-1613
Number of pages11
JournalAdvanced Drug Delivery Reviews
Volume54
Issue number12
DOIs
StatePublished - Dec 7 2002

Keywords

  • Alzheimer's disease
  • Amyloid
  • Immunization
  • Transgenic mice

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