A new study has shed light on the differences between how the immune system responds to Alzheimer's-related inflammation compared to infections.
While inflammation is a key immune response, in Alzheimer's disease, it becomes chronic and harmful rather than short-term and protective. Researchers have been working to understand why this prolonged immune reaction occurs.
The findings, presented at the 69th Biophysical Society Annual Meeting in Los Angeles, highlight crucial variations in immune activity when exposed to Alzheimer’s-related proteins versus bacterial infections.
How the immune system reacts
The research focuses on how immune cells respond to amyloid-beta (Ab) plaques, a defining feature of Alzheimer's, and how this differs from their reaction to bacterial toxins. "Bacteria cannot directly enter the brain due to the blood-brain barrier," explained Arpan Dey, PhD, a postdoctoral associate at the University of Cambridge. "However, small proteins might be mimicking bacterial activity in the brain, triggering inflammation that contributes to dementia."
Dey and his colleagues used immune cell models and exposed them to either Ab aggregates or lipopolysaccharide (LPS), a bacterial toxin that strongly activates immune responses. They specifically studied the formation of myddosomes, structures that play a key role in initiating inflammation.
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Their results showed that larger Ab clusters prompted significant myddosome formation, whereas smaller clusters failed to do so even after prolonged exposure. This suggests that the size of Ab aggregates is a crucial factor in triggering an immune response in Alzheimer’s.
On the other hand, LPS caused a much faster and more intense myddosome reaction than even the largest Ab clumps. This difference in speed and strength may explain why inflammation in Alzheimer’s is persistent and prolonged, whereas infection-related inflammation is typically brief and resolves quickly.
"Our research highlights a fundamental difference in how the brain’s immune system reacts to bacterial infections versus amyloid-beta aggregates," said Dey. "The slower, sustained immune activation in Alzheimer’s may be a key factor in its chronic inflammation."
The researchers now plan to investigate myddosome markers in blood samples from dementia patients and brain tissue from the UK Brain Bank. By uncovering the mechanisms behind Alzheimer’s inflammation, they hope to aid in the development of treatments targeting chronic neuroinflammation.
"This study opens new possibilities for drug discovery," Dey added. "By identifying and targeting inflammatory pathways, we may develop therapies to slow the progression of Alzheimer’s and other neurodegenerative diseases."
Source: with inputs from Indian Media