Research runs rapidly these days. The tools of biotechnology are improving at a pace driven by the computing industry, where progress remains blisteringly fast. Today's researcher can achieve far more and at a much lower cost than the researcher of even ten years ago. Thus new knowledge is rolling in, and every part of the body is yielding up its secrets and surprises: unusually potent stem cells where none were thought to be, a better understanding of how mitochondria actually work, and so on. Amending the textbooks on any aspect of human molecular biology is a quarterly event these days.
Today I noticed two examples of what seem to be fairly significant discoveries in brain biochemistry, of importance to Alzheimer's disease and neurodegeneration in the broader sense. They are illustrative of just how much in the way of important processes may be still be left to discover and integrate into our understanding of our own biology.
In the case of this first study, you might read it while recalling that some researchers argue for Alzheimer's as a form of diabetes, a type 3 diabetes if you like. To the degree that this is the case, Alzheimer's is a largely avoidable fate for most people, just like type 2 diabetes, its prevalence a product of lifestyle choices such as becoming sedentary and putting on weight:
A protein secreted with insulin travels through the bloodstream and accumulates in the brains of individuals with type 2 diabetes and dementia, in the same manner as the amyloid beta Αβ plaques that are associated with Alzheimer's disease. [The] study is the first to identify deposits of the protein, called amylin, in the brains of people with Alzheimer's disease, as well as combined deposits of amylin and plaques, suggesting that amylin is a second amyloid as well as a new biomarker for age-related dementia and Alzheimer's.
"We've known for a long time that diabetes hurts the brain, and there has been a lot of speculation about why that occurs, but there has been no conclusive evidence until now. This research is the first to provide clear evidence that amylin gets into the brain itself and that it forms plaques that are just like the amyloid beta that has been thought to be the cause of Alzheimer's disease."
"We found that the amylin deposits in the brains of people with dementia are both independent of and co-located with the Aβ, which is the suspected cause of Alzheimer's disease. It is both in the walls of the blood vessels of the brain and also in areas remote from the blood vessels. It is accumulating in the brain and we found signs that amylin is killing neurons similar to Αβ. And that might be the answer to the question of 'What makes obese and type 2 diabetes patients more prone to developing dementia?'"
The body defends the brain like a fortress and rings it with a complex system of gateways that control which molecules can enter and exit. While this "blood-brain barrier" was first described in the late 1800s, scientists are only now just beginning to understand the dynamics of how these mechanisms function. In fact, the complex network of waste removal, which researchers have dubbed the glymphatic system, was only first disclosed by [scientists] last August.
The removal of waste is an essential biological function and the lymphatic system - a circulatory network of organs and vessels - performs this task in most of the body. However, the lymphatic system does not extend to the brain. [One] of the reasons why the glymphatic system had long eluded comprehension is that it cannot be detected in samples of brain tissue. The key to discovering and understanding the system was the advent of a new imaging technology called two-photon microscopy which enables scientists to peer deep within the living brain. Using this technology on mice, whose brains are remarkably similar to humans, [researchers] were able to observe and document what amounts to an extensive, and heretofore unknown, plumbing system responsible for flushing waste from throughout the brain.
One of the hallmarks of Alzheimer's disease is the accumulation in the brain of the protein beta amyloid. In fact, over time these proteins amass with such density that they can be observed as plaques on scans of the brain. Understanding what role the glymphatic system plays in the brain's inability to break down and remove beta amyloid could point the way to new treatments. Specifically, whether certainly key 'players' in the glymphatic system, such as astrocytes, can be manipulated to ramp up the removal of waste.
"The idea that 'dirty brain' diseases like Alzheimer may result from a slowing down of the glymphatic system as we age is a completely new way to think about neurological disorders. It also presents us with a new set of targets to potentially increase the efficiency of glymphatic clearance and, ultimately, change the course of these conditions."