At the Jacobs Lab, our work is driven by a bold but clear question:

Can we move Alzheimers detection and prevention to an earlier biological stage than is currently feasible?

Alzheimers disease develops silently, often decades before symptoms appear. Today, most research focuses on detecting amyloid and tau protein accumulation in the cortex of cognitively normal older adults, the so-called preclinical stage of Alzheimers disease Within our lab, we aim to move the timeline even further back. Our goal is to detect the disease at its earliest biological origins before cortical damage emerges in what we call the pre-preclinical stage, beginning as early as midlife. We believe the key to changing the course of Alzheimers disease lies in identifying and protecting the vulnerable brain systems affected before the cortex is involved.

Our work focuses on small but powerful brain regions deep within the brain, known as neuromodulatory subcortical systems. These include the locus coeruleus, basal forebrain, and raphe nuclei. These nuclei provide the brain with important signaling molecules, or neurotransmitters, that regulate essential functions such as attention, memory, mood, and sleep. Importantly, these nuclei are the first regions in the brain that are affected by Alzheimers disease tau pathology, starting early in adulthood.

Using cutting-edge brain imaging methods developed in our lab, we can now visualize these vulnerable brain regions in living individuals in great detail. Our work showed that changes in these nuclei can predict cortical tau accumulation and predict cognitive changes over the next 8 years. Importantly, the health of these systems helps explain why some individuals remain cognitively resilient despite Alzheimers pathology, while others experience subtle early changes in cognition or behavior. 

By combining cutting-edge brain imaging (3T MRI, 7T MRI, and PET) with innovative and scalable tools to measure cognition and behavior, we aim to:

       Detect Alzheimers disease as early as possible, and predict the transition from healthy aging to the earliest signs of preclinical Alzheimers disease

       Understand why the disease progresses differently across individuals: why some remain resilient, and others are at risk

       Inform and develop interventions that protect and strengthen these vulnerable brain systems, and that hopefully can delay disease progression

Our ultimate goal is to shift Alzheimers research and care toward earlier detection, personalized risk assessment, and effective prevention.