title: Invasion of hematopoietic cells into the brain of amyloid precursor protein transgenic mice.
abstract: The significance of the peripheral immune system in Alzheimer's disease pathogenesis remains controversial. To study the CNS invasion of hematopoietic cells in the course of cerebral amyloidosis, we used a green fluorescence protein (GFP)-bone marrow chimeric amyloid precursor protein transgenic mouse model (APP23 mice). No difference in the number of GFP-positive invading cells was observed between young APP23 mice and nontransgenic control mice. In contrast, in aged, amyloid-depositing APP23 mice, a significant increase in the number of invading ameboid-like GFP-positive cells was found compared with age-matched nontransgenic control mice. Interestingly, independent of the time after transplantation, only a subpopulation of amyloid deposits was surrounded by invading cells. This suggests that not all amyloid plaques are a target for invading cells or, alternatively, all amyloid plaques attract invading cells but only for a limited time, possibly at an early stage of plaque evolution. Immunological and ultrastructural phenotyping revealed that macrophages and T-cells accounted for a significant portion of these ameboid-like invading cells. Macrophages did not show evidence of amyloid phagocytosis at the electron microscopic level, and no obvious signs for T-cell-mediated inflammation or neurodegeneration were observed. The observation that hematopoietic cells invade the brain in response to cerebral amyloidosis may hold an unrecognized therapeutic potential.
authors.affiliation: Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany. a.stalder@unibas.ch
authors.forename: Anna K
authors.initials: AK
authors.lastname: Stalder
authors.forename: Florian
authors.initials: F
authors.lastname: Ermini
authors.forename: Luca
authors.initials: L
authors.lastname: Bondolfi
authors.forename: Werner
authors.initials: W
authors.lastname: Krenger
authors.forename: Guido J
authors.initials: GJ
authors.lastname: Burbach
authors.forename: Thomas
authors.initials: T
authors.lastname: Deller
authors.forename: Janaky
authors.initials: J
authors.lastname: Coomaraswamy
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.forename: Regine
authors.initials: R
authors.lastname: Landmann
authors.forename: Mathias
authors.initials: M
authors.lastname: Jucker
mesh_terms: D000682:Amyloid; D017772:Amyloid Neuropathies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D016026:Bone Marrow Transplantation; D001921:Brain / Q000378:metabolism*; D001927:Brain Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement; D049452:Green Fluorescent Proteins; D006410:Hematopoiesis; D008264:Macrophages; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010587:Phagocytosis; D013601:T-Lymphocytes / Q000473:pathology; D018183:Transplantation Chimera
chemical_list: D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D049452:Green Fluorescent Proteins