INTRODUCTION: Alzheimer's disease is the leading cause of disability and poor 
health, takes a huge emotional and financial burden on family caregivers, and is 
costly. Donanemab (LY3002813) is a new monoclonal antibody that uniquely targets 
Aβ(p3-42), a pyroglutamate form of Amyloid-β (Aβ) exclusively found in plaques.
AREAS COVERED: The phase 2 trial of donanemab in participants with early 
symptomatic Alzheimer's disease, TRAILBLAZER-ALZ. Donanemab reduced cerebral 
plaque but not tau load and only marginally improved the primary outcome of 
cognition and activities of daily living (p = 0.04) without altering individual 
measures of these.
EXPERT OPINION: In TRAILBLAZER-ALZ, anticholinesterase use was given at the 
beginning but not the end of the trial, and thus, it is not known whether 
changes in this or other medicines were involved in the outcome with donanemab. 
Tau load (measured with flortuacipir PET) may be a biomarker of cognition but 
was not altered by donanemab. As there is no clear evidence that removing 
cerebral amyloid plaques with Aβ antibodies, such as donanemab, improves 
cognition and the activities of daily living in Alzheimer's disease, clinical 
trials with these agents should be abandoned, and more time and money should 
spend on further investigating the underlying cause of Alzheimer's disease.