1. Comunicação do académico Senhor George Perry, intitulada In Search of a Cure for Alzheimer's Disease.
For nearly four decades, our research has focused on dissecting the cytopathology of Alzheimer’s disease (AD) with the goal of developing a cure. We have used oxidative stress as a window to view and understand AD. Oxidative damage to sugars, proteins, lipids and nucleic acids increases in neuronal cytoplasm. The same neuronal compartment has increased redox-active iron and copper, which can catalyze oxidative damage, and likely derive from mitochondrial debris (in and outside lysosomes) including cytochromes, mitochondria specific prosthetic groups and mtDNA. Mitochondria show altered axonal transport, size distribution, energetics, fusion/fission, and degradation in AD that correlate with the extent of oxidative damage suggesting they are the origin. Surprisingly, amyloidβ and tau are quantitatively associated with reduced neuronal oxidative damage. Copper sequestration by amyloidβ blocks copper mediated oxidation of lipids and vitamin C indicating amyloidβ can be a protective response rather than the initiator of AD. Instead of being bound to amyloidβ, iron is present as 10nm magnetite crystals with super-paramagnetic properties. Not just amyloidβ, but also tau, may be protective responses induced in AD to maintain neurons with altered balance for decades. While these studies put oxidative stress at the center of AD, they also highlight a complexity of multifaceted alterations that is homeostatic and requires a deeper level of understanding before an effective cure.