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Researchers have discovered a protein that protects the brain’s immune cells from age-related decline, potentially leading to future treatments for Alzheimer’s disease.
The protein TIMP2 plays an important role in keeping the immune cells healthy, offering clues about how the brain changes with age. Removing TIMP2 causes these cells, known as microglia, to develop characteristics linked to ageing, according to a study published in the journal Nature Communications by researchers from the Mount Sinai School of Medicine.
When TIMP2 is restored in the bloodstream of older mice, microglia become better at removing cell debris and show fewer molecular signs of inflammation.
The findings suggest TIMP2 may be an important factor in maintaining healthy immune activity in the brain as one ages, researchers say.
While growing older is the biggest known risk factor for Alzheimer’s, scientists still do not fully understand the biological processes that make the ageing brain increasingly vulnerable to such neurological conditions.
A growing body of research focuses on microglia and their link with Alzheimer’s due to their key role in removing cellular waste and helping maintain the networks through which neurons communicate. These cells can lose some of their ability to perform these essential tasks with ageing and shift into states that promote inflammation and interfere with normal brain function.
“TIMP2 facilitates healthy function for the brain’s immune cells,” Joseph Castellano, an author of the study, said.
“By supporting the ability of microglia to clear debris and limit maladaptive responses, TIMP2 may help restore aspects of microglial function that become compromised with age.”
The new study suggests this function sits at the intersection of several processes that are critical for normal brain function.
In the study, scientists assessed mice genetically modified to lack TIMP2 throughout their bodies using several advanced techniques and found striking changes when TIMP2 was absent.
The microglia in these mice developed several features typically associated with ageing and brain injury.
Their ability to remove debris declined and they showed signatures linked to ageing and stress. They also contained higher levels of proteins associated with inflammation and stress in the environment surrounding brain cells.
The findings confirm that TIMP2 helps prevent microglia from shifting towards potentially damaging states.
When TIMP2 was injected into older mice, allowing the protein to circulate throughout the body, the treatment produced encouraging results.
Microglia became more effective at clearing cellular debris and showed a reduction in signs linked to inflammation.
“While additional studies are needed, this work provides new insight into how youth-associated factors influence pathways involved in brain ageing and age-related neurological disorders that may ultimately inform therapeutic strategies,” Dr Castellano said.