Invasion of hematopoietic cells into the brain of amyloid precursor protein transgenic mice.
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.
Stalder
Anna K
AK
Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany. a.stalder@unibas.ch
Ermini
Florian
F
Bondolfi
Luca
L
Krenger
Werner
W
Burbach
Guido J
GJ
Deller
Thomas
T
Coomaraswamy
Janaky
J
Staufenbiel
Matthias
M
Landmann
Regine
R
Jucker
Mathias
M
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
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D049452:Green Fluorescent Proteins