Abstract Body

Objective:
In 2012, the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) Adaptive Prevention Trial platform launched a double-blind, randomized, placebo-controlled, parallel group trial of two anti-amyloid-beta monoclonal antibodies, gantenerumab and solanezumab (NCT01760005) in participants at-risk for or with mild symptoms of dominantly inherited AD (DIAD).
Methods:
DIAN-TU enrolled 194 participants in this phase 2/3 trial testing effects on cognitive, clinical, and biological measures of AD with a common close at 4 years (average 5.2 years) in November 2019. Amendments increased the dose of each drug and extended the study from 2 year biomarker to 4 year cognitive endpoint.
Results:
The findings of drug effects on clinical and cognitive measures, MRI, CSF, blood and amyloid PET scans will be presented for each drug comparing active to placebo and control participants from the DIAN Observational study. The primary cognitive endpoints were not met, however, key secondary outcomes of decreasing amyloid plaques, phospho-tau and neurodegeneration markers were met for gantenerumab. These results inform about AD hypotheses of causation, timing of treatment and the prospect of slowing or preventing AD in DIAD and sporadic AD.
Conclusions:
A remaining challenge in sporadic AD is identifying those who will get dementia and predicting the age of onset. Recent developments of blood-based biomarkers now offer potential accuracy and precision similar to PET or CSF measures of amyloid plaques and tau tangles. These advancements enable the possibility of using simple blood tests to implement treatment and prevention trials faster and with larger numbers of participants, increasing the power to identify effective treatments.