Alzheimer's tied to brain's 'waste removal system'

In Alzheimer's disease, our brains accumulate molecular waste; excess buildup of proteins that could become toxic and disrupt communication between brain cells. A new study asks whether the endolysosomal system, which takes care of cellular waste, may be involved in the development of this condition.

The Alzheimer's Association say that around 5.7 million people in the United States live with Alzheimer's disease.

They estimate that this figure will rise to almost 14 million by 2050.

Despite this disease being so common among the aging population, it remains unclear what exactly causes it.

This means that treatments for Alzheimer's tend to focus on managing the symptoms — such as memory loss, agitation, and disorientation — rather than addressing the root cause.

Recently, researchers from the South Australian Health and Medical Research Institute in Adelaide have investigated whether this condition is tied to the functioning of the endolysosomal system — which takes care of removing "waste material" from cells — when it comes to the brain.

The scientists' hypothesis was rooted in the knowledge that a key characteristic of Alzheimer's and other dementias is the buildup of toxic plaque made of "waste" proteins, such as beta-amyloid and tau.

"But it's not yet certain if these deposits are a cause or a symptom of cognitive decline, or how the disease progresses at the molecular level," explains study co-author Dr. Ville-Petteri Mäkinen.

'Genetic link' with 'waste system'

The researchers note that, as a person's brain begins to age, the endolysosomal system also starts working less efficiently, which may mean that excess brain waste accumulates more easily.

In this recent study — whose findings are now published in the journal Brain — the team was able to identify a link between a set of genes tied to the endolysosomal system and the risk of developing Alzheimer's disease.

"The exciting aspect of our research is that we've now found a genetic link between the genes that comprise the endolysosomal system and Alzheimer's risk," says Dr. Mäkinen.

It is still unclear whether certain gene variations that affect the "waste removal" system are actually involved in causing this form of dementia, but the researchers believe that the possibility is fairly high.

"Because DNA is set at conception and stays the same, genetic variation may affect disease risk but not vice versa; that's why the genetic association we observed can be considered causal evidence," Dr. Mäkinen argues.

'An important step' forward in research

Study co-author Dr. Tim Sargeant adds that the team's findings may open up a new avenue for investigation in Alzheimer's research that could eventually lead to the development of more effective, targeted treatments for the disease.

The problem, he explains, is that available therapy cannot halt the progression of Alzheimer's disease.

"One of the greatest challenges with Alzheimer's," says Dr. Sargeant, "is the lack of effective treatments, or medications to slow progress or stop progression of symptoms."

"This research is an important step in understanding how dysfunction in the brain's recycling machinery may cause Alzheimer's disease, and may be the key to unlocking new drug targets, or treatment strategies."

Dr. Tim Sargeant