Alzheimer's and brain waste removal

A brain affected by Alzheimer's disease is no longer able to properly eliminate its waste, and a new study on mice suggests cholesterol may play a role in this dysfunction. The study highlights how the brain's waste removal system, known as the glymphatic system, appears to be disrupted in Alzheimer's disease.

Glymphatic system disruption

The glymphatic system, which eliminates toxins from the brain, appears to be disrupted in Alzheimer's disease. This is indicated by a study conducted on rodents, whose results have been published in the journal bioRxiv and reported by New Scientist.

Alzheimer's disease impact

Alzheimer's disease affects about 50 million people worldwide, and in these individuals, the disruption of the glymphatic system contributes to the accumulation of two types of harmful proteins: beta-amyloid, which aggregates into plaques, and the tau protein, which forms aggregates called neurofibrillary tangles. The brain then struggles to eliminate these wastes.

Study on mice

Scientists from the Korean Institute of Brain Research compared the gray matter of healthy mice with that of genetically modified mice designed to develop Alzheimer's disease. After injecting a dye into their cerebrospinal fluid, they observed that in healthy individuals, the dye was almost entirely eliminated after two hours.

Dye accumulation

In contrast, in genetically modified rodents, the dye accumulated around the arteries and a small amount reached the brain tissue. This is a sign of glymphatic system dysfunction. In mice carrying mutations linked to Alzheimer's, researchers found that the dye was mainly located in the amyloid plaques, abnormal accumulations of proteins that build up around neurons.

Cholesterol's role

To investigate the role of cholesterol, the scientists analyzed a fluorescent marker that binds to cholesterol in the gray matter of the rodents. In genetically modified mice, the signal increased up to 120 minutes after the staining, while in the other group, the fluorescence decreased after 5 minutes. Cholesterol plays a role in regulating the signaling between neurons.

Cholesterol and transport

According to the researchers, it is possible that cholesterol contributes to the transport of chemicals from the perivascular spaces to the neurons. A mechanism related to the disease could block this transport.

Perivascular spaces as highways

Maiken Nedergaard, a neuroscientist at the University of Rochester in the United States, explains that the perivascular spaces constitute the highway for the rapid entry of fluids. "If this system is impaired, it becomes very difficult to get a substance into the brain," she says.

Future research goals

However, the study does not clearly demonstrate the role of cholesterol in glymphatic function. The researchers are already focused on future experiments, which would allow them to track the circulation of cerebrospinal fluid in real time.