postulated mechanism of therapeutic action (25, 47). Conflicting reports of tarenflurbil effects on Aβ42 in animal models (43–45) and failures to observe changes in Aβ42 in the cerebrospinal fluid (CSF) of normal elderly volunteers after 21 days of treatment (48) should have indicated to the investigators a need for special attention to ensure adequate concentrations of drug in the brain in the phase 3 trial. Because of these and other unresolved issues, this drug and its therapeutic mechanisms cannot be eliminated as potentially beneficial for patients with AD. Investigators may have lost a potential drug, a molecular backbone for further drug developments, and an opportunity to test human brain mechanisms possibly relevant to therapeutic response in AD.
