Visualizing Brain Proteinopathies Using [F-18] Flornaptitril-PET in the Prediction of Clinical Progression of Mild Cognitive Impairment with Either Suspected Chronic Traumatic Encephalopathy or Alzh

This project, titled "Visualizing Brain Proteinopathies Using [F-18] Flornaptitril-PET in the Prediction of Clinical Progression of Mild Cognitive Impairment with Either Suspected Chronic Traumatic Encephalopathy or Alzh[heimer's]," focuses on applying molecular positron emission tomography (PET) imaging with the tracer [F-18] flornaptitril to characterize and visualize brain proteinopathies in individuals with mild cognitive impairment (MCI) who have suspected chronic traumatic encephalopathy (CTE) or Alzheimer's disease (AD). The central purpose is to determine whether in vivo imaging of disease-associated protein aggregates can inform prognosis and predict clinical progression among patients with MCI and overlapping or uncertain etiologies.

Using flornaptitril-PET to detect and map pathological protein deposition offers a noninvasive window into molecular pathology that is otherwise available only at autopsy. By comparing PET signal patterns, distribution, and burden across individuals with suspected CTE-related versus AD-related processes, the study seeks to identify imaging signatures associated with different trajectories of cognitive decline. The project emphasizes longitudinal clinical correlation: imaging findings will be linked to serial cognitive assessments and functional outcomes to evaluate whether baseline or evolving PET markers are predictive of clinical worsening, stabilization, or conversion to dementia. Beyond diagnostic classification, this work aims to refine risk stratification for patients presenting with MCI and ambiguous clinical histories, including those with prior head trauma or mixed risk factors.

The research also explores the potential for flornaptitril-PET to distinguish overlapping proteinopathies and to detect mixed pathology, an important consideration in older adults where multiple neurodegenerative processes frequently coexist. Methodologically, the study centers on standardized PET acquisition and image analysis protocols to quantify tracer retention in target regions implicated in CTE and AD, enabling comparison across participants and timepoints. Imaging results will be interpreted in the context of clinical phenotypes, neuropsychological profiles, and, where available, complementary biomarkers to build an integrated model of disease progression.

If successful, the project could inform clinical decision-making by identifying individuals at higher risk for rapid decline who may benefit from closer monitoring, early therapeutic intervention, or enrollment in clinical trials. It may also contribute to the development of imaging endpoints for treatment studies targeting proteinopathies. Overall, this investigation aims to leverage flornaptitril-PET to improve understanding of the molecular underpinnings of MCI in populations with suspected CTE or AD, to enhance prognostic precision, and to support more personalized approaches to diagnosis, counseling, and management of patients at risk for neurodegenerative progression.