A drug that destroys dementia-causing proteins has been developed by scientists. In mice, it cleared them from the brain - offering hope of reversing age-related cognitive decline. The compound opens the door to treating or even preventing neurodegenerative diseases.
It rejuvenates immune cells surrounding grey and white matter. They sweep out waste - but slow up in people and rodents with Alzheimer's. Senior author Professor Jonathan Kipnis, of Washington University in St Louis, said: "Alzheimer's has been studied for many years from the perspective of how neurons die. But there are other cells, such as immune cells on the periphery of the brain, that also may play a role. It doesn't look likely we will be able to revive dead or dying neurons.
"But the immune cells that sit on the borders of the brain are a feasible target for treating age-related brain diseases. They're more accessible, and could be drugged or replaced. In this study, we treated aged mice with a molecule that can activate aged immune cells.
"It worked in improving fluid flow and waste clearance from the brain. This holds promise as an approach to treating neurodegenerative diseases."
In Alzheimer's, rogue proteins known as amyloid beta and tau clump together, killing neurons. They trigger the tell-tale symptoms of memory loss and confusion. The chemicals have also been linked to Parkinson's. Finding a way to get rid of them is a potential gamechanger.
Prof Kipnis and colleagues identified key immune cells called macrophages that cleanse the brain's vessels. Lead author Dr Antoine Drieu, from the same lab, explained: "Cerebrospinal fluid flow is impaired in numerous neurodegenerative diseases such as Alzheimer's, stroke, Parkinson's and multiple sclerosis. If we can restore fluid flow through the brain just by boosting these macrophages, maybe we can slow the progression of these diseases. It's a dream, but who knows? It might work."
Further analysis revealed the macrophages are altered in Alzheimer's patients. The immune cells are less able to consume and dispose of waste. The US team found those most important are scarce in older mice. So they administered a protein that boosted their activity.
The immune cells started behaving more like those from younger mice. Further, the treatment improved fluid flow and waste clearance from the rodents' brains. Prof Kipnis said: "Collectively, our results show macrophages could potentially be targeted pharmacologically to alleviate brain clearance deficits associated with ageing and Alzheimer's disease.
"I'm discussing with colleagues how we can replace or rejuvenate those cells in ageing brains and as a treatment for Alzheimer's. I hope one day we will be able to slow down or delay the development of age-related brain diseases with this approach."
Prof Kipnis is an expert in the blossoming field of neuroimmunology, the study of how the immune system affects the brain. In 2015, he discovered a network of vessels that drains fluid, cells and small molecules from the brain into the immune system's lymph nodes.
Last year, his team showed some investigational Alzheimer's therapies are more effective in mice when paired with a treatment geared toward improving drainage of fluid and debris from the brain. Prof Kipnis directs a program supported by a $15 million grant from the National Institutes of Health (NIH).
It explores how macrophages and other immune cells interact with fluid flow and drainage in the brain during ageing. The number of dementia cases worldwide will soar to more than 150 million by 2050. There is no cure.
