title: Hematopoietic MyD88-adaptor protein acts as a natural defense mechanism for cognitive deficits in Alzheimer's disease.
abstract: Accumulating evidence supports a critical role of Toll-like receptors in the clearance of Amyloid beta (Aβ) by microglial cells. Myeloid differentiation factor 88 (MyD88) is an adaptor protein that bridges the intracellular signal to nucleus for most of these innate immune receptors. We investigated here the role of competent MyD88 hematopoietic stem cells on the cognitive decline of a mouse model of Alzheimer's disease (AD). We generated classical chimeric mouse models using irradiation and transplantation of wild type GFP cells and MyD88-deficient cells. Transplantation of GFP cells essentially rescued the cognitive impairment, whereas MyD88-deficient cells significantly accelerated memory deficits of APP(swe)/PS1 mice. Moreover, we found that monocytes and microglia deficient for MyD88 exhibit a functionally impaired phagocytic reaction to Aβ.
authors.affiliation: Laboratory of Endocrinology and Genomics, CHUQ (CHUL) Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier boul., Québec, Canada G1V 4G2.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Michaud
authors.forename: Karine L
authors.initials: KL
authors.lastname: Richard
authors.forename: Serge
authors.initials: S
authors.lastname: Rivest
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D003071:Cognition; D003072:Cognition Disorders / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007113:Immunity, Innate; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000502:physiology; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010587:Phagocytosis; D015398:Signal Transduction
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88