Emerging prospects for the disease-modifying treatment of Alzheimer's disease

Lary C. Walker, Chris C. Ibegbu, Charles W. Todd, Harriet L. Robinson, Mathias Jucker, Harry LeVine, Sam Gandy

Research output: Contribution to journalComment/debate

47 Scopus citations

Abstract

The currently approved therapies for Alzheimer's disease (AD) in the US are designed to modify the function of specific neurotransmitter systems in the brain. While these palliative treatments can benefit some patients for a period of time, they do not halt the relentless cognitive and behavioral deterioration that characterize this neurodegenerative disorder. Consequently, much current research on AD is directed toward illuminating the disease process itself, particularly the abnormal accumulation of certain proteins in brain: the amyloid-β protein (Aβ) in senile plaques and cerebral blood vessels, and the tau protein in neurofibrillary tangles. Genetic, biochemical and pathologic evidence now favors a primary role of Aβ aggregation in the Alzheimer proteopathic cascade, and studies in mice indicate that lowering the amount of this protein in brain can be beneficial. Recently, Aβ-immunization therapy has emerged as a particularly promising therapeutic option for treating Alzheimer's disease, but unexpected treatment-related side-effects are an overriding issue. These adverse events were not anticipated from preclinical studies with rodents; hence, more biologically relevant models, such as nonhuman primates, are needed to test the safety and efficacy of novel therapies for Alzheimer's disease.

Original languageEnglish
Pages (from-to)1001-1008
Number of pages8
JournalBiochemical Pharmacology
Volume69
Issue number7
DOIs
StatePublished - Apr 1 2005

Bibliographical note

Funding Information:
We gratefully acknowledge Stephanie Stephens and Hanie Elfenbein for expert technical assistance, and Margaret L. Walker for helpful comments. This work was supported in part by a grant from the Woodruff Foundation to LCW and by NIH grant RR-00165.

Keywords

  • Amyloid
  • Cerebral amyloid angiopathy
  • Primate
  • Proteopathy
  • Senile plaque
  • Tau
  • Transgenic mice
  • Vaccination

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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