Microglia contribute to the propagation of Abeta pathology into healthy brain tissue

The extracellular accumulation of amyloid-beta (A?) peptides is a major hallmark of Alzheimer's disease (AD). It is widely accepted that microglia associate with A? plaques and appear morphologically activated especially in their immediate vicinity. Whether microglia play a role in A? plaque formation and contribute to the propagation of A? pathology remains however unknown. We therefore investigated the characteristics of microglia during neural transplantation experiments where wild-type neurons are grafted into the cortex of AD mouse models. Here, we demonstrate that A? from the transgenic host tissue is able to enter and deposit within wild-type (WT) grafts, a process that is accompanied by massive microglia infiltration. Notably, manipulation of microglia function or microglia elimination significantly reduced A? deposition within the grafts. Similarly, time-lapse in vivo two-photon imaging revealed that microglia transport A? to the site of injury thereby identifying microglia as cellular carrier of A? that propagate A? pathology in previously unaffected CNS tissue. Our data thus argue for a hitherto unexplored mechanism of A? propagation. Overall design: examination of gene profile of microglia isolated from cortical grafts and non-grafted tissue