Evaluating the Potential Therapeutic Role of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers for Alzheimer's Disease using a Drosophila Model

Presenilins (PS) play a role in familial Alzheimer's disease (AD) and Notch signalling. In a genetic screen looking for modifiers of APP but not Notch, we identified Drosophila orthologs of Angiotensin Converting Enzyme (ACE). Interestingly, ACE polymorphisms are associated with AD and Apo-E, the best characterized risk factor for late-onset AD. Moreover, ACE inhibitors (ACE-I) delayed the onset of cognitive impairment and neurodegeneration in mice and humans. However, it remains unclear why ACE-I are beneficial in AD. Here, we explore the link between PS and ACE in a Drosophila model using genetics and pharmacology. We found that ACE disruption does not affect Notch related phenotypes. Moreover, we found that ACE-I and Angiotensin Receptor Blockers are beneficial in an AD Drosophila model. Since inhibition of ACE has no detrimental effects on Notch and modulates AD related phenotypes, it could provide an important therapeutic target for AD.M.Sc