Gene linked to Alzheimer’s disease may lead to new therapeutic targets

Microglia, immune-regulating brain cells, have long been implicated in the progression of Alzheimer’s disease (AD). A recent study from Brigham and Women’s Hospital delves into the genetic aspect of microglia and its contribution to neuroinflammation, a key factor in AD.

The researchers identified that a reduction in INPP5D, a gene present in microglia, leads to neuroinflammation, heightening the risk of AD. This discovery carries significant implications for developing microglia-focused therapeutics for AD and related disorders, as detailed in their publication in Nature Communications.

Dr. Tracy Young-Pearse, the corresponding author from the Department of Neurology at Brigham and Women’s Hospital, emphasized the importance of understanding the molecular mechanisms governing the relationship between microglia and neuroinflammation. Pinpointing specific genes involved in this process can pave the way for targeted therapeutics.

Detecting neuroinflammation is crucial in neurodegenerative diseases, particularly in the early stages of AD. Microglia play a clear role in this process, yet the molecular pathways remain elusive. The research team utilized various experimental approaches to explore the connection between INPP5D levels and a specific type of brain inflammation known as inflammasome activation.

In their analysis of human brain tissue from AD patients and a control group, lower INPP5D levels were found in AD tissues, correlating with activated inflammation. Additionally, using human brain cells derived from stem cells, the researchers identified specific proteins within microglia that, when inhibited, could block inflammasome activation.

While this study represents a comprehensive analysis of INPP5D in the AD brain, questions persist about whether INPP5D should be targeted with therapeutics. The researchers acknowledge the complexity of INPP5D activity in AD brains, emphasizing the need for future studies to determine if targeting INPP5D can prevent cognitive decline in AD patients.

Dr. Young-Pearse noted the promising potential of INPP5D but stressed the necessity for further exploration. Future studies examining the interplay between INPP5D activity and inflammasome regulation are deemed essential to enhance our understanding of microglia in AD and develop a comprehensive toolbox of therapeutics targeting various molecular pathways leading to AD.

Source: Brigham and Women’s Hospital

Leave a Comment