Characterization of a Drosophila Alzheimer's Disease Model: Pharmacological Rescue of Cognitive Defects

摘要: Transgenic models of Alzheimer's disease (AD) have made significant contributions to our understanding AD pathogenesis, and are useful tools in the development potential therapeutics. The fruit fly, Drosophila melanogaster, provides a genetically tractable, powerful system study biochemical, genetic, environmental, behavioral aspects complex human diseases, including AD. In an effort model AD, we over-expressed APP BACE genes central nervous system. Biochemical, neuroanatomical, analyses indicate that these flies exhibit clinical neuropathology symptomology. These include generation Aβ40 Aβ42, presence amyloid aggregates, dramatic neuroanatomical changes, defects motor reflex behavior, memory. addition, external morphological abnormalities. Treatment with γ-secretase inhibitor suppressed phenotypes. Further, all phenotypes present within first few days adult fly life. Taken together data demonstrate this transgenic can serve as tool for identification therapeutic interventions.