Recent research has uncovered a mechanism that hinders microglia from effectively clearing misfolded amyloid-β, the protein aggregates implicated in Alzheimer’s disease. This process involves the interaction between APOE and the LILRB4 receptor on microglia, which can be impacted by different APOE variants linked to Alzheimer’s risk. Scientists have shown that disrupting this interaction restores microglia’s ability to clear amyloid-β.
Toxic protein clumps in the brain are a hallmark of various neurodegenerative diseases, including Alzheimer’s. Microglia typically surround these clumps to contain their spread and eliminate them. However, in Alzheimer’s, this clearance process is inhibited, partly due to the binding of APOE proteins in the clumps to the LILRB4 receptor on microglia. By blocking this interaction, researchers were able to activate microglia and enhance clearance of amyloid plaques in mouse models.
Following amyloid plaque formation, tau tangles develop in neurons, leading to cognitive decline. High levels of LILRB4 and APOE have been detected in advanced Alzheimer’s stages, suggesting a role in disease progression. Future studies will explore the effects of blocking this interaction on tau-related pathology.
Link: https://medicine.wustl.edu/news/immunotherapy-for-alzheimers-disease-shows-promise-in-mouse-study/
