Zhao et al. Molecular Neurodegeneration (2017) 12:47
Microglia limit the expansion of β-amyloid plaques in a mouse model of Alzheimer’s disease
Ruohe Zhao1,2, Wanling Hu1, Julia Tsai2, Wei Li1,2* and Wen-Biao Gan1,2*
Background: Microglia are known as resident immune cells in the brain. β-amyloid (Aβ) plaques in the brain of
Alzheimer’s disease (AD) are surrounded by microglia, but whether and how microglia affect the formation and
maintenance of plaques remains controversial.
Methods: We depleted microglia by injecting diphtheria toxin (DT) in CX3CR1CreER/+:R26DTR/+ (CX3CR1-iDTR) mice crossed with APPswe/PSEN1dE9 (APP/PS1) mice. Intravital time-lapse imaging was performed to examine changes in the number and size of Congo Red-labeled amyloid plaques over 1–2 weeks. We also examined spine density and shaft diameter of dendrites passing through plaques in a PSAPP mouse model of AD (PS1M146L line 6.2 × Tg2576) crossed with Thy1 YFP H-line mice.
Results: We found that DT administration to CX3CR1-iDTR mice efficiently ablated microglia within one week and that
microglia repopulated in the second week after DT administration. Microglia depletion didn’t affect the number of
amyloid plaques, but led to ~13% increase in the size of Aβ plaques within one week. Moreover, microglia repopulation
was associated with the stabilization of plaque size during the second week. In addition, we found dendritic spine loss
and shaft atrophy in the distal parts of dendrites passing through plaques.
Conclusion: Our results demonstrate the important role of microglia in limiting the growth of Aβ plaques and
plaque-associated disruption of neuronal connection.
Keywords: Alzheimer’s disease, Aβ plaque, Microglia depletion, Two-photon imaging, APP/PS1, CX3CR1CreER/+:R26DTR/+