A study published in the journal Neuron has found that the protein KAT7 may play an important role in the development of inflammatory processes in the brain associated with Alzheimer's disease by promoting the pathological activation of microglia, the immune cells of the central nervous system.

Using animal models and analyses of postmortem brain samples from individuals with Alzheimer’s disease, researchers discovered that increased KAT7 activity was associated with heightened neuroinflammation and worsening cognitive function.

The scientists found that KAT7 acts as an epigenetic regulator that influences gene activity in microglia. Elevated KAT7 activity increased the expression of the protein CMPK2, leading to greater production of mitochondrial DNA and its leakage into the cell cytoplasm.

This DNA “leakage” triggered innate immune inflammatory mechanisms, including the cGAS-STING and NLRP3 signaling pathways. While these pathways normally help protect the body, their chronic activation can contribute to neuronal damage.

As a result, microglia entered a persistently activated inflammatory state, increasing damage to brain tissue, disrupting synaptic function, and potentially accelerating cognitive decline.

Both animal models of Alzheimer’s disease and human brain samples showed elevated activity of components of the KAT7 signaling complex, as well as epigenetic modification markers associated with its function.

Importantly, suppressing KAT7—either through genetic deletion in microglia or pharmacological inhibition using the experimental compound WM-3835—led to a significant reduction in brain inflammation. In animal models, researchers observed decreased amyloid burden, improved synaptic plasticity, and better performance in memory and learning tests, including the Morris water maze.

These findings suggest that KAT7 keeps microglia in a state of chronic inflammatory “readiness,” thereby amplifying neuroinflammation and worsening Alzheimer’s pathology.

Blocking KAT7 may therefore represent a promising therapeutic strategy for reducing inflammation and improving cognitive function, at least in preclinical models.