floating-point asked: What's your opinion on the origins of Alzheimer's disease (tau vs. beta amyloid as causative)? Also, it seems that cholesterol plays a role in the disease based on epidemiological and genetic association studies (APOE e4 mutations). What's your view on the biochemical basis for this? Perhaps an impact on APP processing at the membrane level?
These are really fantastic questions! I do not have a ton of insight into the field as it really doesn’t align with my research. This makes me much less partial than others perhaps. I do find it very interesting, so I have read up on it though.
For those who don’t know, Alzheimer’s can only be truly diagnosed post mortem, when you can see neurofibrillary tangles (tau) build up inside neurons and beta amyloid plaques outside the cells, both seeming to contribute to the widespread neurodegeneration (brain matter deterioration) that causes the observed changes in patients with Alzheimer’s.
There are people in either camp of the “which comes first/ which affects Alzheimer’s brains the most” as far as tau or amyloid beta goes. There was a paper back in 2008 (I believe- maybe early 2009) where they attempted to vaccinate against amyloid beta in people with very early stage Alzheimer’s and found that it did prevent amyloid beta build up in some patients, but did not slow or prevent the progression of Alzheimer’s. It had been highly successful in mouse models of Alzheimer’s and was very disappointing. It lent a lot of hope to the people in the tau camp, but it doesn’t mean that amyloid beta would not be causing Alzheimer’s. There may have been something caused by the vaccine that led to plaques being toxic when broken down or it could be that since they only administered to patients who already had some symptoms that it was too late… it isn’t clear.
The APOE e4 mutations is also interesting. As is your question on how it seems to impact APP. I am going to save these for another post so that this one doesn’t become too dense/long. Look for it later this week!!
Thanks again for the great questions!!
