Alzheimer’s disease may have triggers outside the brain, study suggests

14:05

By: Azzat Manal

Alzheimer’s disease may have triggers outside the brain, study suggests

Scientists are gaining new insights into the mechanisms behind Alzheimer’s disease, with new research suggesting that some of the immune processes involved in brain damage may be initiated outside the brain.

Researchers at Washington University School of Medicine reached the finding after studying genetically modified mice that developed Alzheimer’s-like disease. Their experiments indicate that certain immune cells accumulating in the brain may be activated by other immune cells located in lymph nodes and tissues elsewhere in the body.

The discovery could broaden the way researchers understand Alzheimer’s and potentially open new avenues for treatment. Hao Hu, a postdoctoral researcher at Washington University and the study’s lead author, said the findings suggest that Alzheimer’s should be viewed as a disease involving the entire body rather than focusing exclusively on changes occurring inside the brain.

Alzheimer’s is the most common form of dementia and is traditionally associated with the accumulation of abnormal forms of amyloid-beta and tau proteins in the brain. While amyloid-beta has long been considered one of the main drivers of the disease, recent research has highlighted the complexity of the condition and the limited benefits provided by some current anti-amyloid treatments.

The Washington University team has previously investigated another potential contributor to neurological damage: T cells, a type of immune cell that can accumulate in the brain during Alzheimer’s-like disease. Earlier experiments suggested that reducing or blocking the activity of these cells could decrease inflammation and limit additional damage to brain tissue.

The researchers then turned their attention to dendritic cells, which normally help activate T cells. Because relatively few dendritic cells are found in the brain, the team investigated whether the cells responsible for stimulating the T-cell response might originate elsewhere in the body.

In the latest experiments, researchers genetically removed dendritic cells from lymph nodes and other tissues outside the brain in the mice. This intervention appeared to prevent the abnormal accumulation of T cells in the brain and was associated with less neurological damage.

The animals also maintained normal cognitive function despite the intervention. Notably, the improvement occurred without reducing the amount of abnormal tau protein in their brains, suggesting that the immune response could contribute to disease-related damage independently of tau accumulation.

The findings remain preliminary because the research was conducted in mice. Further studies will be required to determine whether the same immune pathways operate in people with Alzheimer’s disease.

Researchers also still do not know exactly what initially activates dendritic cells and prompts them to direct T cells toward the brain. The team suspects that abnormal tau accumulation could play an important role in initiating this process.

The researchers now plan to investigate whether targeting dendritic cells later in life can still reduce brain damage in older mice. They also intend to examine whether targeting specific lymph nodes could provide therapeutic benefits while minimizing potential side effects.

If the mechanism is confirmed in future studies, the research could contribute to a broader understanding of Alzheimer’s and encourage treatments that address interactions between the immune system and the brain rather than focusing exclusively on protein deposits within the brain.