This will be a very #streamsofconsciousness post where I ramble a bit about my work.

As I’ve said before I study Amyloid Beta in Alzheimer’s disease. I am very new to this field, so much of what is surprising to me might be old hat to the experts. But I’m quite flummoxed on what exactly Amyloid Beta is doing both in diseased and healthy brains. When I started this job, I read papers indicating that Amyloid Beta (henceforth AB) forms these large filaments, and like a bull in a china shop those large filaments will sort of knock around and cause damage. Damaging the brain in that way is obviously a hazard, and would lead to exactly the type of neuro-degeneration that is a hallmark of Alzheimer’s disease.

So because of this, it’s my job to extract these large AB filaments and take pictures of them. That way we can see exactly what they look like and why it is that they do so much damage. But then this simple picture changed. AB is made up of thousands of individual peptides, and I read papers saying these individual peptides might actually be what causes the disease by disrupting the neurons and causing them to die. But if that’s the case, then what are the filaments doing? Are they still causing damage by being big and huge, or are they entirely benign and a red herring? If they are benign, then my studying them and taking pictures of them might be leading us down a dead end.

And now I found that AB is also necessary for the development of a healthy brain. Now this in itself is not too out there, any medicine can turn into poison if the dose is wrong. So this could easily be too much of a good thing, or a good thing in the wrong place, that while normally AB helps a brain, in Alzheimer’s disease something has gone wrong to cause AB to kill nerve cells. But still it’s surprising.

The paper I read indicates that AB is necessary for process of synaptic plasticity. No time to get into the whole details, but synaptic plasticity underlies the formation of memories in the brain. Mice who do not have AB have a harder time forming memories and completing tasks than mice with AB. So now I’m at the point where actually AB is necessary for the formation of memories of a healthy brain, but then sOmEtHiNg happens and it caused Alzheimer’s disease, which is characterized by deficiencies in memories. So what is happening?!?!?

I… don’t know. I don’t know if anyone knows. But I wish I had the tools to study this further. The difficulty is that I’m not sure if I do. My setup is geared towards looking at those giant AB filaments I talked about earlier. Filaments have a big, rigid form and you can do structural analysis on them to get what is essentially a 3D model. But all these papers talking about the role of AB in healthy brains, they are talking about it in the small monomeric form. Small monomers don’t form rigid structures in quite the same way, they are more akin to a floppy noodle, there’s no rigid form to hang your hat on and so no clean 3D model can be made for them. So maybe I’m using the wrong tool for the wrong job. Or maybe it really IS the filaments that are doing the damage. I’m just not sure at this time and it’s racking my brain trying to know where I should go next.