The biochemistry of Alzheimer's disease is complex, and the tools available to researchers only recently up to the task of deciphering it all. Understanding the way in which the condition develops is still an ongoing work in progress:
Amyloid fibrils can form the foundations of huge protein deposits - or plaques - long-seen in the brains of Alzheimer's sufferers, and once believed to be the cause of the disease, before the discovery of "toxic oligomers" [a] decade or so ago. A plaque's size and density renders it insoluble, and consequently unable to move. Whereas the oligomers, which give rise to Alzheimer's disease, are small enough to spread easily around the brain - killing neurons and interacting harmfully with other molecules - but how they were formed was until now a mystery.
The new work [shows] that once a small but critical level of malfunctioning protein "clumps" have formed, a runaway chain reaction is triggered that multiplies exponentially the number of these protein composites, activating new focal points through "nucleation". It is this secondary nucleation process that forges juvenile tendrils, initially consisting of clusters that contain just a few protein molecules. Small and highly diffusible, these are the "toxic oligomers" that careen dangerously around the brain cells, killing neurons and ultimately causing loss of memory and other symptoms of dementia.
"We are essentially using a physical and chemical methods to address a biomolecular problem, mapping out the networks of processes and dominant mechanisms to 'recreate the crime scene' at the molecular root of Alzheimer's disease. With a disease like Alzheimer's, you have to intervene in a highly specific manner to prevent the formation of the toxic agents. Now we've found how the oligomers are created, we know what process we need to turn off."