Researchers are looking at different approaches to tackling amyloid beta and tau protein aggregations in the brain to treat Alzheimer’s disease. A new study published in Nature found that activating immune cells present at the brain’s border could increase the clearance of toxic wastes, opening new treatment avenues for Alzheimer’s.
“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 in Alzheimer’s,” professor Jonathan Kipnis, the senior author of the study, said in a statement.
Researchers have identified that deposition of amyloid beta and tau proteins in the brain is the leading cause of a decline in memory and cognitive function in older people and those with neurodegenerative diseases like Alzheimer’s, Parkinson’s disease, and dementia.
Earlier in 2015, the research team from the Washington University School of Medicine in St Louis, USA, discovered that the central nervous system had a network of vessels around the brain and central nervous system called the meningeal lymphatic system. This lymphatic system works like a drain, helping to flush out toxins from the brain. However, they also found that if this lymphatic drainage system is affected or damaged, it contributes to neurodegenerative disease progression.
In a 2021 follow-up study, the same team observed how lymphatic vessels flushed out the toxins into the blood. They found that with age and neurodegenerative disease, the lymphatic vessels weaken, thereby impacting the efficiency of eliminating unwanted toxic wastes from the brain and the flow of cerebrospinal fluid in the brain’s outer layer. In addition, the fluid contains immune cells called parenchymal macrophages, which help flush out toxins.
To investigate if strengthening the lymphatic vessels affected the flushing out mechanism, the researchers experimented on two groups of mice: one was given an anti-Alzheimer drug and the other a growth protein to strengthen the lymphatic vessels along with the drug. They observed that the group given the strengthening protein and anti-Alzheimer’s drug showed a better clearance of toxins from the brain than the group given only the medication.
In the present study, Prof Kipnis’ team further investigated the activity of the damaged parenchymal macrophages in aged mice and with Alzheimer’s condition. “If we can restore fluid flow through the brain just by boosting these macrophages (immune cells), maybe we can slow down the progression of these diseases,” said postdoctoral fellow and lead author of the study, Antonie Drieu, in a statement.
When they activated these macrophages, the regulation of cerebrospinal fluid improved, and the flushing out of the toxic wastes from the brain increased.
“It doesn’t look likely that 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,” Dr Kipnis said. Due to their ease of access, it is easy to activate these immune cells, thus opening the doors for possible therapeutic targets for the neurodegenerative disease, he added in the statement.