A current article, published on this year’s solstice (21 Dec), has excited Alzheimer’s researchers about the possibility of a refinement of the line of attack on the disease. The deposit of amyloid plaques is widely regarded as the core cause of the death of masses of brain neurons, the direct cause of Alzheimer’s symptoms. Most drug development efforts have targeted removal of the plaques, and almost all have failed (see The hard truth about Alzheimer’s drugs, link filed in Treatment > Drugs). The only one with any promise is Aducanumab, which only seems to have value if taken in very early stages of Alzheimer’s, and will be hugely expensive (see the article at end).
Besides the development of amyloid plaques, tangles of tau proteins inside the neurons, together with signs of activated/irritated immune cells called microglia are also found extensively in the brains of Alzheimer’s patients. The activated/irritated microglia can be caused by such things as a mild injury or a virus, and are also provoked by the deposit of amyloid. The newly published paper suggests that there may be an interaction or even feedback loop between deposit of amyloid and the irritated microglia. A key part of the process is the formation inside the microglia of a protein complex called an inflammasome. This complex both signals to other microglia to provoke further inflammation, but also releases specks of a protein called ASC. These specks appear to act as seeds for further deposit of amyloid, and the resulting amyloid plaques have ASC specks at their core. The first media article below compares this to the “grit inside a pearl”.
The research was mostly carried out on mice, though examining the brains of deceased Alzheimer’s patients showed substantial amounts of amyloid plaque containing ASC specs at core. In parts of the mice experiments, it was shown that presence or absence of ASC affected the generation of amyloid, and in other parts of the experiments, it was shown that when antibodies to ASC were injected, it interfered with the seeding effect for amyloid by ASC.
Thus, attacking inflammation and the action of ASC now seems like a promising way forward.
Here are two media articles about the study:
Brain inflammation sows the seeds of Alzheimer’s
Do Microglia Spread Aβ Plaques?
Here is the original study article:
Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s disease
All three of these links have been added to Alzheimers > Neurology & Neuroplasticity
And here is an article about the drug Aducanumab (link added to Treatment > Drugs):
Robert Chen, MD-PhD candidate in Alzheimer’s research: What were the key findings from the Aducanumab phase 1 clinical trials? [Reprinted as: Aducanumab Is Showing Promise As An Alzheimer’s Treatment, But It’s Still Early]