Longevity & AgingGut Macrophages Drive Parkinson's Spread from Intestine to Brain
A Nature 2026 study reveals that muscularis externa macrophages (ME-Macs) — immune cells lining the gut wall — play a central role in initiating and spreading α-synuclein (αS) pathology from the enteric nervous system to the brain in Parkinson's disease models. ME-Macs engulf misfolded αS, develop endolysosomal dysfunction, and activate T cells that migrate through the dura mater into the CNS. Crucially, targeted depletion of ME-Macs using anti-CSF1R and anti-CCR2 antibodies injected into the muscularis reduced αS accumulation in both gut and brain, blocked T cell trafficking, and improved motor function and neuronal survival in mouse models — positioning ME-Macs as early cellular drivers of body-first Parkinson's disease.
