Dissecting the pathological effects of human A 40 and A 42 in Drosophila: A potential model for Alzheimer’s disease

Accumulation of amyloid(A ) 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 A 40 or A 42 peptide in the Drosophila brain can induce pathological phenotypes resembling AD. The expression of A 42 led to the formation of diffused amyloid deposits, age-dependent learning defects, and extensive neurodegeneration. In contrast, expression of A 40 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 A 42 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 A toxicity and the discovery of novel therapeutic targets for AD.