Shining a Light on How Early Tau-Related Brain Changes Affect Memory Loss

This project delves into the brainstem’s role in early tau accumulation and memory loss via advanced magnetic resonance imaging, plasma biomarkers, and long-term data, enhancing our understanding of Alzheimer’s progression.

This project spotlights previously understudied brain regions—tiny nuclei in the brainstem—that are the starting point of Alzheimer’s-related tau accumulation and investigates how their changes contribute to memory loss. Using innovative brain imaging techniques, blood-based biomarkers, and memory assessments collected over a decade from a large number of participants, this project improves our understanding of the time course of neural changes in later life and their mechanistic role in the earliest stages of Alzheimer’s development.

The proposed project puts a spotlight on previously understudied brain regions that form the starting point of Alzheimer’s-related tau accumulation and how their changes contribute to memory loss. Using MRI, plasma biomarkers, and behavior densely sampled over a decade in large samples of participants, it advances our understanding of the temporal trajectory of late-life neural changes in the brainstem and their mechanistic role in the earliest stages of Alzheimer’s development.

The proposed project closes an important gap in the literature by (1) estimating person-specific change in several brainstem structures and (2) determining how this relates to the buildup of disease biomarkers and hippocampal memory loss in older participants at risk for sporadic Alzheimer’s. Moreover, this project puts an emphasis on improving the reliability of MRI of the brainstem, which will help qualify these measures as imaging biomarkers for early-stage Alzheimer’s pathologic changes.