Amyloid-β and Tau: the Trigger and Bullet in Alzheimer’s Disease Pathogenesis
Dr. George Bloom; University of Virginia
November 30 at 12:20pm in the Fralin Auditorium, Fralin Hall room 102
Hosted by Carla Finkelstein
George Bloom is a Professor of Biology, Cell Biology and Neuroscience, and Chair of the Department of Biology at the University of Virginia (UVA). Trained as a cell biologist, he has a long track record studying fundamental aspects of cellular behavior, such as microtubule and actin filament assembly, membrane trafficking and cell motility. During the past dozen years, however, his lab has transformed into a research center that emphasizes a cell biological approach to study neurodegeneration, most notably seminal processes that convert healthy neurons into Alzheimer’s disease (AD) neurons. One important outcome of that effort has been the elucidation of a pathogenic signaling network that connects soluble, cytosolic forms of amyloid-β and tau, the respective building blocks of the insoluble plaques and tangles that accumulate in AD brain. Dr. Bloom earned a BA in Biology and History, and a PhD in Biology from the University of Pennsylvania, and then received postdoctoral training at the University of North Carolina at Chapel Hill and the Worcester Foundation for Experimental Biology (since merged with the University of Massachusetts Medical School). Beginning in 1984, he rose through the faculty ranks at the University of Texas Southwestern Medical Center at Dallas, where he finally served as a Professor in the Department of Cell Biology before moving to UVA in 2000. Dr. Bloom has been on grant review panels for the NIH, the Alzheimer's Association, the American Cancer Society and the Department of Defense. He is a AAAS Fellow, an Associate Editor for the journals, Journal of Alzheimer's Disease and Cytoskeleton, and a former Zenith Fellow of the Alzheimer’s Association.
The defining features of Alzheimer's disease (AD) include conspicuous changes in both brain histology and behavior. AD brain is characterized microscopically by the combined presence of two classes of abnormal structures, extracellular amyloid plaques and intra-neuronal neurofibrillary tangles, both of which comprise insoluble, densely packed filaments. The soluble building blocks of these structures are amyloid-β (Aβ) peptides for plaques and tau for tangles. Aβ peptides are proteolytic fragments of the transmembrane amyloid precursor protein (APP), whereas tau is a brain-specific, axon-enriched microtubule-associated protein. The behavioral symptoms of AD correlate with the accumulation of plaques and tangles, and are a direct consequence of the damage and destruction of synapses that mediate memory and cognition. Synapse loss can be caused by the failure of live neurons to maintain functional axons and dendrites, or by neuron death. During the past dozen years, a steadily accumulating body of evidence has indicated that soluble forms of Aβ and tau work together, independently of their accumulation into plaques and tangles, to drive healthy neurons into the diseased state, and that hallmark toxic properties of Aβ require tau. George Bloom's seminar will highlight his lab's work aimed at unraveling the Aβ-induced, tau-dependent signaling pathways that cause AD.