Alzheimer's Disease Considered as Synaptic Imbalance

From Maria Konovalenko: "I met Dr. Bredesen during the Buck Advisory Council meeting at the Buck Institute for Research on Aging in Novato, California on May 21. [The] Advisory Council consists of influential individuals who can contribute to Buck Institute's mission of advancing aging research. A very interesting crowd. ... Dale Bredesen opened the mini conference with his report on Alzheimer's research. The majority of scientists envision this horrible degenerative process as accumulation of toxic molecules, namely amyloid beta and tau proteins. Amyloid beta forms plaques between the cells and tau protein tangles inside the cells. These toxic proteins disrupt the functions of our neurons. ... So, Dr. Bredesen views Alzheimer's disease differently - as an imbalance between synaptic maintenance and synaptic reorganization. The thing is that for our brain to function properly we need to form connections between our neurons, and also we need to break down those connections that we no longer need. According to Dale Bredesen, this balance disrupts, it shifts towards synaptic reorganization, we loose our memory, face the horrors of loosing our consciousness and eventually we die. ... So how can we preserve this balance? Dr. Bredesen's lab studies the underlying mechanisms of neurodegeneration. There were able to find out that one of the things that contributes to the balance shift is the change in APP cleavage. APP is amyloid precursor protein. It is concentrated in synapses of our neurons. APP can break down into either two, or four parts. When it breaks down into 2 parts those proteins are sAPP alfa and CTF alfa. This is a 'good' combination. However, during aging amyloid precursor protein cleavage shifts towards the 'bad' combination, which is sAPP beta, Amyloid beta, Jcasp and C31. This is the shift in balance that leads to the onset of disease. The shift can be restored. The mouse strain that has one mutation that leads to not having APP to break down to Jcasp and C31 proteins leads to restoring memory in mice. But the most exciting thing is that Dr. Bredesen is testing a drug that shifts the APP cleavage balance back to normal."



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