12/06/2024

Network-based analyses uncover how neuroinflammation-causing microglia in Alzheimer’s disease form
The study strengthens the connection between changes in microglia and Alzheimer’s disease and identifies drugs that may stop or reverse these changes.

Cleveland Clinic Genome Center researchers have unraveled how immune cells called microglia can transform and drive harmful processes like neuroinflammation in Alzheimer’s disease. The study, published in Alzheimer’s & Dementia: The Journal of The Alzheimer’s Association, also integrates drug databases with real-world patient data to identify FDA-approved drugs that may be repurposed to target disease-associated microglia in Alzheimer’s disease without affecting the healthy type.

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Microglia in Alzheimer’s disease
Microglia are specialized immune cells that patrol our brains, seeking and responding to tissue damage and external threats like bacteria and viruses. Different types of microglial cells use different methods to keep our brains safe. Some may cause neuroinflammation – inflammation in our brains – to fight invaders or kickstart the repair process in damaged cells. Others may work to “eat” dangerous substances in our brains, and clean up damage and debris.

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An FDA-approved drug holds promise to treat harmful microglia in Alzheimer’s disease
The team’s network-based analyses identified three unique subtypes of harmful microglia that promoted disease progression. Each of these subtypes had their own genetic signatures that drove unique behaviors to support Alzheimer’s disease. For example, one microglial subtype causes harmful neuroinflammation, while another supports the buildup of proteins in our brains that cause Alzheimer's, like tau.

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