Researchers at the VIB-KU Leuven Center for Brain & Disease Research have discovered that microglia, the immune cells of the brain, play opposing roles at different stages of Alzheimer’s disease. The study, led by the Bart De Strooper Lab and published in Nature Communications, provides new insights into how these cells influence amyloid-β (Aβ) plaques, a key hallmark of Alzheimer’s.
Microglia’s role in Alzheimer’s has long puzzled scientists, with conflicting studies suggesting they either help clear Aβ plaques or contribute to their spread. To investigate, the researchers used a drug to deplete microglia in mouse models of Alzheimer’s at different stages of the disease.
They found that in early stages, microglia promote plaque formation, as depleting them before plaques formed resulted in fewer plaques. However, in later stages, microglia appeared to play a protective role by compacting plaques and reducing neuronal damage, as plaque pathology worsened when microglia were removed after plaques had already formed.
Further experiments using human microglia transplanted into the mice confirmed these findings. Homeostatic (inactive) microglia caused larger and more numerous plaques along with increased neuronal damage, while activated microglia helped limit pathology in later stages.
“Our study shows that microglia are detrimental in early Alzheimer’s by promoting plaque formation but play a beneficial role later by containing plaque damage,” explained Bart De Strooper, senior author of the study.
As reported by medicalxpress, this research resolves conflicting reports about microglia’s role in Alzheimer’s and underscores their importance as drivers of disease progression. It also highlights the need for stage-specific therapeutic approaches targeting microglia to improve patient outcomes.