Researchers have discovered a previously unknown structure in the brains of individuals affected by Alzheimer's disease. This finding could potentially help understand why the disease continues to progress, even with treatments targeting more well-known plaques.
The study analyzed samples from human and mouse brains, leading to the identification of a new type of aggregation associated with mitochondrial function, which is responsible for cellular energy supply.
What are mitochondrial plaques?
Alzheimer's disease is the most common form of dementia, affecting approximately 57 million people worldwide, with projections indicating this number will exceed 150 million by 2050.
Traditionally, the disease has been linked to the accumulation of beta-amyloid plaques and altered tau proteins, which leads to neuronal death and impairment of memory, learning, and thought.
However, a recent study published in Nature Neuroscience points to another critical factor—so-called mitochondrial plaques. These arise when mitophagy, the mechanism responsible for clearing damaged mitochondria, malfunctions.
This discovery establishes mitochondrial plaques as a previously unrecognized characteristic of Alzheimer's disease. Paul Robbins, a biochemist from the University of Minnesota and one of the study's authors, noted this in his commentary.
How did researchers arrive at the discovery?
The team utilized genetically modified mice and donor human brain tissue for analysis. A fluorescent marker called Keima was used to monitor mitochondrial behavior, capable of indicating different stages of this process.
The analysis showed that mitochondrial plaques can appear both independently and alongside beta-amyloid plaques. Key findings of the study include:
- Plaques appeared in young mice;
- Accumulation increased with the animals' age;
- Neither structure was found in healthy brains;
- The highest concentration was observed in neuronal axons and dendrites.
Researchers also observed that lysosomes, which are responsible for clearing cellular debris, attempt to break down this material but become overloaded as the plaques grow.
The discovery may expand treatment options
Another aspect captured the team's attention. Unlike beta-amyloid plaques, which are located outside nerve cells, mitochondrial plaques appear to directly affect areas responsible for signal transmission between neurons.
Siuli Dan, a cell biologist from the University of Minnesota and the study's first author, explained: 'Unlike amyloid plaques found outside brain cells, these plaques seem to directly impact neurons, making them a new potential target for Alzheimer's disease treatment.'
The researchers emphasize that therapies focused solely on clearing beta-amyloid plaques are not always capable of halting neurodegeneration. The identification of this new type of pathology strengthens the hypothesis that Alzheimer's disease results from the simultaneous action of various processes.
Future research is expected to investigate treatment methods that combine the fight against beta-amyloid plaques and mitochondrial plaques, as well as preserving mitophagy. The authors also suggest that these structures could serve as a new biomarker for tracking disease progression.
