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I lead the Laboratory for Early Alzheimer’s Disease Symptoms (LEADS), an NIH-funded translational and clinical research program. Our overarching hypothesis is that understanding early symptoms of Alzheimer’s disease (AD) can improve its detection, monitoring, and treatment. To accomplish this, we utilize a “bench-to-bedside” approach than spans two interrelated groups to study mechanisms, risk factors, and biomarkers of how early symptoms relate to cognitive outcomes.

At the bench, we interrogate neural circuit compromise related to early AD symptoms and cognitive outcomes using ex vivo and in vivo opto-electrophysiology and imaging, behavior, -omics, and computational techniques in transgenic models, as well as analysis of postmortem human brain tissue. At the ��ɫtv Alzheimer’s Disease Research Center, I lead the Clinical Core to study these same symptoms and circuits in a longitudinal study of older adults. Our approach combines neurocognitive phenotyping, sensorimotor assessments, as well as imaging (MRI, PET) and biofluid (CSF, plasma) markers of amyloid, tau, neurodegeneration, vascular, and other processes. I also lead several therapeutic trials for early AD.

Ongoing projects that relate to our overarching goal include:

• Neural circuitry related to the earliest cognitive signs of AD
• Mechanisms and clinical utility of anxiety as an early sign of AD
• Mechanisms and clinical utility of sensory dysfunction (olfaction, vision) as an early sign of AD
• The relationship of early symptoms to cognitive outcomes in at-risk groups
• The relationship between cerebrovascular disease, early AD, and cognitive outcomes
• Application of artificial intelligence to identify early AD symptoms, determine related risk factors, and predict cognitive outcomes

In addition to the NIH, LEADS has been additionally supported by the NSF, Alzheimer’s Association, BrightFocus Foundation, Leon Levy Foundation, and the Blas Frangione Foundation.