The Challenge
Did BACE inhibitor dosing drive cognitive decline — and could alternative dosing enable safer early intervention?
BACE inhibitors were developed to reduce amyloid production and tested in multiple large-scale trials, including early and preclinical populations. Despite a strong biological rationale, these trials were halted for lack of efficacy or adverse outcomes, leaving open questions about timing, patient selection and mechanism. Historically each trial was analyzed in isolation; by harmonizing and reanalyzing data across trials, this project enables a more complete evaluation of treatment effects in early-stage populations — to inform future prevention strategies and better trial design.
Our Approach
The project applies the AD Data Initiative's model of unlocking high-value datasets and enabling secure, scalable analysis through AD Workbench, where researchers run reproducible workflows without moving sensitive data. Operating as a consortium of academic, nonprofit and industry partners, it combines previously siloed trial data to revisit questions no single study could answer — whether prior outcomes reflect true lack of efficacy or limits of design, duration or population.
Harmonizing data from more than 10 BACE and γ-secretase inhibitor trials for greater statistical power than ever achieved.
Key Research Questions
01
Is the cognitive decline seen with BACE inhibitors an on-target (Aβ-related) or off-target effect?
02
If off-target, can molecules or populations be optimized to mitigate cognitive worsening?
03
If on-target, is there a level of BACE inhibition that lowers Aβ enough for benefit while remaining safe for chronic dosing?
Representative questions, not a comprehensive list.
Partners & Investigators
Leads & steering
Partner institutions
Data & Tools
AD Workbench
Secure cloud analysis where researchers run reproducible workflows without moving data.
