Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance.
Microglial cells aggregate around amyloid plaques in Alzheimer's disease, but, despite their therapeutic potential, various aspects of their reactive kinetics and role in plaque pathogenesis remain hypothetical. Through use of in vivo imaging and quantitative morphological measures in transgenic mice, we demonstrate that local resident microglia rapidly react to plaque formation by extending processes and subsequently migrating toward plaques, in which individual transformed microglia somata remain spatially stable for weeks. The number of plaque-associated microglia increased at a rate of almost three per plaque per month, independent of plaque volume. Larger plaques were surrounded by larger microglia, and a subset of plaques changed in size over time, with an increase or decrease related to the volume of associated microglia. Far from adopting a more static role, plaque-associated microglia retained rapid process and membrane movement at the plaque/glia interface. Microglia internalized systemically injected amyloid-binding dye at a much higher rate in the vicinity of plaques. These results indicate a role for microglia in plaque maintenance and provide a model with multiple targets for therapeutic intervention.
Bolmont
Tristan
T
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany.
Haiss
Florent
F
Eicke
Daniel
D
Radde
Rebecca
R
Mathis
Chester A
CA
Klunk
William E
WE
Kohsaka
Shinichi
S
Jucker
Mathias
M
Calhoun
Michael E
ME
D000682:Amyloid / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology*; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors
D000682:Amyloid