Guest Speaker - 

Fei Yin, PhD, University of Arizona

Discussion - 

Title: Lipid Catabolism in Alzheimer’s Disease: from Mechanism to Therapeutic Strategy

Abstract: Disrupted lipid metabolism and abnormal lipid droplet (LD) buildup are now recognized as key features of Alzheimer’s disease (AD). Genetic studies and clinical evidence further implicate lipid-related pathways as major modifiers of AD risk. Yet, how these lipid changes emerge and subsequently drive disease progression has remained unclear. Our recent work identifies a key role for astrocytes, neurons’ primary support cells, in regulating fatty acid (FA) breakdown and maintaining lipid balance. We find that astrocytic mitochondria are essential for degrading FAs and preventing LD accumulation. When astrocytes become overloaded by lipids, excess acetyl-CoA fuels inflammatory signaling through STAT3 acetylation, leading to astrocyte reactivity and neuroinflammation. Meanwhile, neurons, which normally rely on astrocytes to eliminate surplus or damaged FAs, attempt to degrade FAs themselves. This maladaptive response increases ROS production and oxidative stress and worsens neuronal vulnerability. We also show that amyloid pathology and the APOE4 risk allele disrupt this neuron-astrocyte coupling by impairing FA transfer and degradation and amplifying LD accumulation. Therapeutically, boosting FA degradation specifically in astrocytes reduces lipid buildup, neuroinflammation, and cognitive decline in an AD mouse model. Together, these findings point to lipid catabolism, and particularly astrocytic FA degradation, as a therapeutic target for sustaining brain lipid homeostasis and mitigating neurodegeneration.

Attendance Options - 

If you can't make the seminar in person, you can always join us virtually!

JOIN ZOOM