Genetic link between microglia and Alzheimer’s disease inflammation

Investigators from Brigham and Women’s Hospital, have unveiled a pivotal connection between genetic changes in microglia, immune-regulating brain cells, and the inflammatory response associated with Alzheimer’s disease (AD)

The research, published in Nature Communications, highlights the role of a specific gene, INPP5D, within microglia and its influence on neuroinflammation. It offers promising insights for developing targeted therapeutics for Alzheimer’s and related disorders.

Microglia’s role in Alzheimer’s disease

Microglia are known to play crucial roles in both the healthy and diseased brain, yet the molecular mechanisms governing their relationship with neuroinflammation have remained largely elusive.

The study, led by corresponding author Tracy Young-Pearse, PhD, from the Department of Neurology at Brigham and Women’s Hospital, aimed to unravel these complexities and potentially pave the way for effective treatments.

The researchers discovered that a reduction in the levels of the INPP5D gene in microglia contributes to neuroinflammation, significantly elevating the risk of developing Alzheimer’s. Neuroinflammation is a key factor in the progression of neurodegenerative diseases like Alzheimer’s, and early detection is crucial for timely intervention.

INPP5D reduction linked to neuroinflammation

The team’s findings emphasise the importance of understanding specific genes involved in neuroinflammation to develop targeted therapeutics.

Using a combination of experimental approaches, the researchers explored the relationship between INPP5D levels and inflammasome activation, a component involved in the inflammatory process.

Analysing human brain tissue from Alzheimer’s patients and a control group, they observed lower levels of INPP5D in Alzheimer’s tissues, correlating with increased inflammation.

Experiments with living human brain cells derived from stem cells provided insights into the molecular interactions within microglia, highlighting specific proteins that could be targeted to inhibit inflammasome activation.

Unravelling the complexity of INPP5D in Alzheimer’s brains

While this study represents the most comprehensive analysis of INPP5D in the Alzheimer’s brain, the researchers acknowledge the complexity of INPP5D activity. Further studies are needed to determine if targeting INPP5D with therapeutics can effectively prevent cognitive decline in Alzheimer’s patients.

These findings mark a significant step forward in understanding the genetic underpinnings of neuroinflammation in Alzheimer’s, offering hope for the development of targeted treatments that could potentially revolutionise the management of this devastating disease.

As research continues, the focus on unravelling the intricate molecular pathways within microglia opens new possibilities for therapeutic interventions that could alter the course of Alzheimer’s disease.