Connections between neuroinflammation and Alzheimer's disease finds new study

Immune-regulating brain cells known as microglia are known to play a role in the progression of Alzheimer's disease (AD). Study by Brigham investigators revealed how genetic changes in certain types of brain cells may contribute to the inflammatory response seen in Alzheimer’s disease

A new study by investigators from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, explores how the genetics of microglia contribute to neuroinflammation and, in turn, AD.

The team revealed that a reduction of INPP5D, a gene found in microglia, results in neuroinflammation and increases the risk for AD. Their results, which have important implications for the design of microglia-centered therapeutics for Alzheimer’s disease and related disorders, are published in Nature Communications.

They found lower levels of INPP5D in the tissues of patients with AD and when INPP5D was reduced, it activated inflammation. In parallel, they used living human brain cells derived from stem cells to study the intricate molecular interactions within microglia that mediate inflammatory processes with a reduction of INPP5D. These studies identified specific proteins that could be inhibited to block inflammasome activation in microglia.

“Our results highlight an exciting promise for INPP5D, but some questions still remain,” said Young-Pearse. “Future studies examining the interaction between INPP5D activity and inflammasome regulation are essential to improve our understanding of microglia in AD and to help develop a comprehensive toolbox of therapeutics that can be deployed to treat each of the molecular roads that lead to AD.

Reference: Chou, V et al. “INPP5D regulates inflammasome activation in human microglia” Nature Communications. DOI: https://doi.org/10.1038/s41467-023-42819-w