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Dr. Fernanda de Felice

Event Start: Jan 05, 2016 1:00 pm
Location: Botterell Hall, Room B139

Dr. Fernanda G. De Felice
Associate Professor
Head, Laboratorio de Doencas Neurodegenerativas
Federal University 
Rio de Janeiro, Brazil 

Inflammation and defective insulin signaling as molecular links between Alzheimer’s disease and Diabetes 

Compelling preclinical and clinical evidence supports a pathophysiological connection between Alzheimer’s disease (AD) and Type 2 diabetes (T2D). Altered metabolism, inflammation and insulin resistance are key pathological features of both diseases. For many years, it was generally considered that the brain was insensitive to insulin, but it is now accepted that this hormone has central neuromodulatory functions, including roles in learning and memory, that are impaired in AD. However, until recently the molecular mechanisms accounting for brain insulin resistance in AD have remained elusive. We investigated the role of AD-associated Ab oligomers in defective brain insulin signaling and memory impairment using mice models of AD and macaques receiving Ab oligomer infusions. We found that Ab oligomers activate the stress sensitive kinases PKR and JNK in a TNF-a-dependent manner, resulting in eIF2a-P, neuronal insulin receptor substrate (IRS-1) inhibition, synapse loss, and memory impairment. Bolstering insulin signaling protected the brain from the deleterious effects of Ab oligomers in mice and macaques. Our results reveal pathogenic mechanisms shared by AD and T2D and establish that a pro-inflammatory signaling mediates defective insulin signaling and memory loss in experimental models of AD.

Tuesday, January 5, 2016
1:00 - 2:00pm
Botterell Hall, Rooom B139