Could Rejuvenating Mitochondria Help Fight Alzheimer's? Study sheds light - Video

Although scientists still do not know the exact cause of Alzheimer's disease, most agree that the disease is characterized by the clumping of certain proteins -beta-amyloid and tau-in the brain.

In a study published in the journal GeroScience, scientists examined how the accumulation of large protein clumps in the brain, called insoluble proteins, in general, might accelerate Alzheimer’s disease.

Protein clumping happens when proteins in the brain stick together in the wrong way. In Alzheimer's disease, two types of proteins, beta-amyloid and tau, are involved. Beta-amyloid forms sticky plaques outside brain cells, blocking their communication and causing inflammation. Tau proteins, which normally help support brain cells, form tangles inside the cells, disrupting their function.

These plaques and tangles damage the brain, leading to the memory loss and confusion seen in Alzheimer's disease.

In the study, researchers, using a worm model, discovered that beta-amyloid causes a massive amount of insolubility in other proteins, especially in a subset of proteins researchers called “the core insoluble proteome.”

The insoluble proteins found in the core insoluble proteome have already been linked to other neurodegenerative conditions including Parkinson’s disease and Huntington’s disease, according to the researchers.

Next, researchers wanted to find a way to potentially undo how beta-amyloid makes proteins insoluble. They noticed that many mitochondrial proteins become insoluble as people age and when beta-amyloid is present. So, they thought that improving the quality of mitochondrial proteins might help counteract some of the harmful effects of beta-amyloid.

These findings suggest that beta-amyloid likely causes many proteins, especially those in mitochondria, to become insoluble. This problem with proteins is similar to changes seen in aging.

The discovery that targeting mitochondrial health can mitigate some of these aging effects suggests a potential novel approach to addressing Alzheimer’s disease.

“It has been known for some time that mitochondria can be negatively impacted by [beta-amyloid] but we show that this is likely due to protein insolubility. Luckily, cells possess a way to recycle damaged mitochondria through a process called mitophagy. Our lab and others study a small molecule that boosts mitophagy to rejuvenate mitochondria. We reasoned that using a pharmacological approach to clear away the insoluble proteins from mitochondria could prevent some of the toxic effects of [beta-amyloid] and that’s exactly what we found,” said the study authors.

Reference: Anderton, E., Chamoli, M., Bhaumik, D. et al. Amyloid β accelerates age-related proteome-wide protein insolubility. GeroScience (2024). https://doi.org/10.1007/s11357-024-01169-1