Emerging Themes in Alzheimer’s Disease Research: Paradigm Shift in Drug Discovery
Todd E. Morgan and Grant A. Krafft
Annual Reports in Medicinal Chemistry (2002) Vol. 37, Chapter 4

The paradigm shift from blocking Ab plaques and fibrils to blocking small soluble Ab toxins such as ADDLs represents a reversal in dogma and an opportunity for generating highly effective AD therapeutics. It has taken more than 90 years to accumulate compelling scientific evidence to support Alzheimer’s original supposition that plaques are not the cause of AD. Clear evidence implicating ADDLs as the molecular pathogens in AD sets the stage for therapeutics that can block AD progression, prevent AD onset, and most importantly, potentially reverse existing AD deficits.