I think in the end the tangles will turn out to be an effect of, and not a cause of, AD. The tubular structures that make up the tangles serve as a sort of skeleton for the neuron and its axons. When the neuron is alive and healthy these tubules are well organized. I think the tangles are the product of a neuron that is dying or dead and the tubules retract from the axons, which can be very long, and tangle in the process. I think the plaques will turn out to be a similar phenomenon. For example, let's say a virus takes over a neuron; the neuron may then produce an abnormal protein, instead of the protein it is designed to produce. Something like this happens in other cells when a virus takes over. One example I can think of is when a rhinovirus (the common cold) takes over cells in the respiratory tract - there is an incredible amount of mucus produced by these cells. In the case of AD, the neuron is not functioning normally, and therefore may not produce the protein that it normally would produce, but instead produces an abnormal protein that then accumulates outside of the cells. This protein may be toxic to other neurons and worsen the situation but may not be the original cause of the situation (AD.) As we age, neurons are going to die and where do the remnants go? How would they be removed from the brain, which is different in so many ways from our other organs. The cells of the bowel slough off into the intestine and are carried away when they die. There isn't a similar mechanism for this to happen in the brain. All of this is just my opinion only, no proof.