This lecture is one of the 2023 Senior Vice Chancellor’s Research Seminar series.

Speaker

Tharick Pascoal, MD, PhD

Associate Professor of Psychiatry and of Neurology, School of Medicine

Topic

Glial Reactivity Plays a Key Role in the Progression of Alzheimer’s Disease

Registration for the lecture is required to receive event instructions.

Topic Overview:

For many years, clinical research on Alzheimer’s disease has primarily focused on the link between the disease’s hallmark pathological features—amyloid and tau proteins—and neurons. Glial cells, which are essential for maintaining neuronal function and play a pivotal role in the human brain’s immune response, have been largely overlooked in clinical studies. The prevailing hypothesis that glial abnormalities are merely secondary phenomena of Alzheimer’s disease’s primary features, amyloid and tau, has resulted in therapeutic interventions targeting glial pathology being underexplored.

In this lecture, Pascoal proposes a paradigm shift, providing evidence that disturbances in glial cells, like astrocyte reactivity and microglial activation, are key upstream determinants of Alzheimer’s disease progression.

The first part of the presentation will underscore the role of astrocyte reactivity in disease onset, demonstrating how it instigates the initial tau pathology before cognitive symptoms appear. The second part will delve into the pivotal role activated microglia play in the subsequent spread of the initial tau pathology across the brain cortex, leading to neuronal degeneration and, eventually, dementia symptoms.

These findings suggest that glial abnormalities should not be dismissed as mere consequences but recognized as key determinants of Alzheimer’s disease progression. Therefore, the abnormalities should be incorporated into the biological definition of the disease, heralding a new era of therapies targeting the neuroimmune system to halt Alzheimer’s disease progression.