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Despite repeated announcements of breakthroughs in Alzheimer's disease and related
dementias (ADRD) research, the stark reality remains that there have been no substantial
advancements in treatments. These failures in clinical translation are in large part
due to a systemic dependence on a flawed framework based on validating preclinical
findings using animal experimentation. In particular, researchers are repeatedly incentivized
by funding programs toward dominant reductionist frameworks (e.g., amyloid-, tau-centric)
and xenogenic research (e.g., transgenic and chimeric models). Here we present an
integrated program of impact studies, research protocols and policy proposals that
aim to address the stagnation in ADRD research, ethical issues and clinical outcomes
by advancing new multi-scale human-based approaches.
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