Alzheimer's Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disorder and remains without curative treatment. While amyloid and tau pathology have long dominated the field, growing evidence indicates that neuroinflammation plays a central role in disease progression. Although innate immune responses—particularly microglia—have been extensively studied, the contribution of adaptive immunity, and T cells in particular, remains poorly understood.

Postmortem studies and cerebrospinal fluid (CSF) analyses suggest that activated CD8⁺ T cells are present in the brains and CSF of patients with AD. However, there are currently no clinical technologies that allow non-invasive detection of T cell involvement in living patients. Our goal is to change that.

Our Approach

In collaboration with CellSight Technologies Inc., we are investigating the use of [¹⁸F]F-AraG as an imaging biomarker of adaptive immune involvement, particularly activated T cells, in AD. Using total-body PET imaging, we aim to:

• Quantify intracerebral [¹⁸F]F-AraG uptake in patients with AD
• Compare tracer biodistribution between AD patients and healthy controls
• Assess systemic T cell activity across lymphoid organs and peripheral tissues 

Furthermore, blood–brain barrier (BBB) breakdown and altered cerebral blood flow are well-established features of AD. Because tracer uptake in the brain can reflect both vascular factors and cellular activation, we apply dynamic imaging and kinetic modeling to separate these effects. 

This study represents the first effort to validate a T cell–specific imaging biomarker for adaptive immunity in Alzheimer’s Disease. 

Alzheimer’s Disease as a Systemic Immune Disorder

Emerging evidence suggests that AD is not confined to the brain. Peripheral immune dysfunction and altered communication between central and systemic immune compartments are increasingly recognized as contributors to disease progression. Total-body PET uniquely enables us to investigate these broader systemic alterations.

A Multi-Center Collaborative Study

This project is part of a multi-center clinical research study led by CellSight Technologies Inc., with three imaging sites:

• University of California, Davis (PI: N Omidvari)
• Washington University at St. Louis (PI: A Chaney)
• Palo Alto Veteran’s Affairs (PI: M Vasanawala)

Broader Impact

The ability to non-invasively quantify both intracerebral and systemic T cell involvement in living patients could transform our understanding of Alzheimer’s disease. If successful, this approach may:

• Provide the first imaging biomarker of adaptive immunity in AD
• Enable patient stratification for immune-modulating therapies
• Guide development and monitoring of immunotherapy-based interventions
• Establish a clinic-ready, noninvasive method for studying immune–neural interactions 

Funding:

R44 AG094397, PI: J Levi

UC Davis Subaward PI: N Omidvari