GRK2 aggregation reveals a new pathway in Alzheimer's disease

A finding that reorients Alzheimer's understanding: aggregation of serine-670-phosphorylated GRK2 appears in brains of mice and dementia patients, where it triggers mitochondrial dysfunction independently of well-known amyloid plaques and tau tangles. Researchers showed that both beta-amyloid and tau induce this GRK2 pathology, which in turn aggregates TOMM6 (a translocase of the outer mitochondrial membrane) and amplifies neuronal damage. The critical insight: reversing this cascade through small molecules that restore monomeric GRK2 and accelerate its proteasomal degradation prevented neuronal loss and improved survival in mouse models, while GRK2 inhibitors caused neurotoxicity. For the longevity-minded reader, this suggests future GRK2-targeted therapies could act where anti-amyloid antibodies have shown limited effects, opening a complementary strategy against age-related neurodegeneration.