title: Microfluidic chemotaxis platform for differentiating the roles of soluble and bound amyloid-β on microglial accumulation.
abstract: Progressive microglial accumulation at amyloid-β (Aβ) plaques is a well-established signature of the pathology of Alzheimer's disease, but how and why microglia accumulate in the vicinity of Aβ plaques is unknown. To understand the distinct roles of Aβ on microglial accumulation, we quantified microglial responses to week-long lasting gradients of soluble Aβ and patterns of surface-bound Aβ in microfluidic chemotaxis platforms. We found that human microglia chemotaxis in gradients of soluble Aβ42 was most effective at two distinct concentrations of 23 pg.mL(-1) and 23 ng.mL(-1) Aβ42 in monomers and oligomers. We uncovered that while the chemotaxis at higher Aβ concentrations was exclusively due to Aβ gradients, chemotaxis at lower concentrations was enhanced by Aβ-induced microglial production of MCP-1. Microglial migration was inhibited by surface-bound Aβ42 in oligomers and fibrils above 45 pg.mm(-2). Better understanding of microglial migration can provide insights into the pathophysiology of senile plaques in AD.
authors.affiliation: BioMEMS Resource Center, Massachusetts General Hospital, Harvard Medical School, USA.
authors.forename: Hansang
authors.initials: H
authors.lastname: Cho
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wong
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hori
authors.forename: Levi B
authors.initials: LB
authors.lastname: Wood
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Zhao
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Haigis
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.forename: Daniel
authors.initials: D
authors.lastname: Irimia
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D002633:Chemotaxis / Q000276:immunology*; D006801:Humans; D044085:Microfluidics / Q000379:methods*; D017628:Microglia / Q000276:immunology*; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; C111835:CCL2 protein, human; D018932:Chemokine CCL2