(continued from Morning session 1)

Back from bagels and coffee.

Bill Mobley (Stanford) began with the bold claim that all neurodegenerative illnesses are ultimately breakdowns of neural circuitry — if not etiologically, then symptomologically. He went on to summarize and review the body of evidence supporting the view that axonal dysfunction contributes to Alzheimer’s Disease (AD) pathology, focusing especially on the idea that decreases in neurotrophic factor signaling and retrograde transport play a causative role in AD. The talk concluded with breathtaking tomography and fluorescence video microscopy of intact circuits manipulated in culture.

Mobley turned over the microphone to a collaborator (Tony Wyss-Coray) who argued that age- and AD-related changes in autophagy (e.g., decreases in the level of the autophagy protein beclin) could explain how receptors and transport factors might get “stuck” in axons, further contributing to pathology and neurodegeneration. Consistent with this, both Aß plaque deposition and APP accumulation are dramatically increased in beclin+/- mice. The collaborator was senior author of the recent paper about a serum cytokine profile of AD, and he said some more about the possibility that the factors shown to be associated with AD are actually contributing to disease pathology.

Changing gears from the brain to the pancreas (half the LLHF’s mission is devoted to diabetes), Alberto Hayek and C. C. King from the Whittier Institute for Diabetes described efforts to derive populations of insulin-producing beta cells, suitable for transplant, from stem cells and other sources. Quick version: So far, not so good, but researchers are learning a ton about the basic regulatory biology of pancreatic cells (especially the miRNA, proteomic and epigenetic/methylation profiles of beta cells), and hopes are high that at some point in the not-too-distant future, stem cell-based approaches will indeed fulfill their oft-cited promise in potential treatments for diabetes.

(continued in Afternoon session)