Transcription
You may have heard about this big study that recently released that implicates elemental lithium in preserving and even reversing signs of devastating cognitive condition Alzheimer's disease. Well, we went over it here too, including the clinical data in humans, but I'd like to take you a layer deeper in understanding exactly how lithium is proposed to defend our brain cells against Alzheimer's disease.
Because there's a few different ways and they largely hinge on one devious enzyme, GSK3. The thing is, lithium, a mineral, can correct a major problem in Alzheimer's disease called long-term potentiation. LTP, as the cool kids call it, is, in very simple terms, the capacity for your neurons, your brain cells, to strengthen their connections with one another. This is a key consequence of Alzheimer's disease: reduced LTP.
Now, this mischievous enzyme GSK3 is a tagging protein, a little like the games of tag played as a kid. It literally touches other proteins within your cells and adds a tag called phosphorylation and changes their activity and function. Well, one of its targets is called a tau protein. Tau is a stabilizing protein. So its function is to stabilize the highways running across your neurons. Again, those are brain cells. These highways, more correctly called microtubules, allow the cell to move different discrete packages from one end to the other. Think of it like dump trucks carrying construction equipment to other sections of the cell. These highways remain stable and functional if they are bound and secured by tau proteins.
Now, the issue in Alzheimer's is that these tau proteins can be hyper tagged, like an annoying brat tagging everyone over and over, although they know that they've been tagged. We get it, Justin. I'm it. When tau is hyper tagged or hyperphosphorylated, by the technical term, it scrunches up and creates tangles. Essentially, it doesn't stabilize the microtubules, the highway, anymore and it forms these aggregates of proteins that are stuck together inside the cell. So you can imagine that if GSK3 is hypertagging tau, we begin to see Alzheimer's issues. The main point here is that an enzyme called GSK3 destabilizes the brain cells as well as encourages tangles of proteins to build up inside the brain cells.
Still, that isn't all that GSK3 is implicated in relation to Alzheimer's because you may have heard of beta-amyloid plaques being involved in Alzheimer's disease. These are clumps of proteins that are found outside of the neurons and interfere with neuronal communication. Well, for those protein clumps to get there, they have to be secreted by brain cells. And guess what influences their secretion? That's right, good old GSK3. Essentially, your cells will make more amyloid precursor proteins, abbreviated APP, which get released from the cell and accumulate in these amyloid plaques. That all happens because these enzymes called secretases process or cut the APP to be released out of the cell. So, the greater activity of these particular secretases, the worse. And it just so happens that GSK3 doesn't act on the secretases itself, but it will tag the APP, the amyloid precursor proteins. And that tag makes the environment around the APP more attractive for the secretases, which leads them to be more active in processing and secreting the APP to form the plaques. Pretty wild, isn't it?
So we've gone over two mechanisms by which this enzyme GSK3 encourages Alzheimer's disease. In this last case, GSK3 makes for a friendlier environment for amyloid beta plaque formation. Now, how should we think about lithium fitting into all this? Well, it just so happens that lithium binds and inhibits GSK3 directly, among several other ways of inhibiting this GSK3 enzyme. And while GSK3 obviously has multiple ways that it promotes Alzheimer's disease, which, by the way, if you have a family history, this enzyme is particularly active, as the plaques produced can further stimulate GSK3, like bratty kids egging on bratty kids to do mischievous things. Anyway, lithium stops GSK3.
Still, there's much more that I go over on lithium's direct effects on GSK3, along with an interesting interaction with magnesium, and I go into the most effective types of lithium in my full analysis and in another in-depth analysis on lithium, which is included for the Physionic Insiders, along with all these perks right over here. The link to join the insiders is in the description if you're interested.
But what should we make of all this? Regardless of these GSK3 mechanisms and how lithium could reduce these tau tangles and from destabilizing the brain cells and also stop the processing of these beta-amyloid precursor proteins that inhibit brain cell-to-cell communication, long-term potentiation, and so on. I don't think that lithium is the only cure to all of Alzheimer's. There's likely other issues to address. However, elemental lithium has been shown in human studies to reduce and preserve brain function in people not yet with Alzheimer's and people developing Alzheimer's. So, these aren't small fish that we're talking about here. If you want more on the human research and the broader implications of lithium in Alzheimer's, check it all out right here.