Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Department of Life Science, National Tsing Hua University, Hsinchu 30043, Taiwan.
Department of Functional Genomics, Novartis Institute for Biomedical Research, Novartis Pharmaceuticals, 556 Morris Avenue, Summit, NJ 07901, USA.
Accumulation of amyloid-ß(Aß) peptides in the brain has been suggested to be the primary event in sequential progression of Alzheimer's disease (AD). Here, we use Drosophila to examine whether expression of either the human Aß40 or Aß42 peptide in the Drosophila brain can induce pathological phenotypes resembling AD. The expression of Aß42 led to the formation of diffused amyloid deposits, age-dependent learning defects, and extensive neurodegeneration. In contrast, expression of Aß40 caused only age-dependent learning defects but did not lead to the formation of amyloid deposits or neurodegeneration. These results strongly suggest that accumulation of Aß42 in the brain is sufficient to cause behavioral deficits and neurodegeneration. Moreover, Drosophila may serve as a model for facilitating the understanding of molecular mechanisms underlying Aß toxicity and the discovery of novel therapeutic targets for AD.