Invasion of hematopoietic cells into the brain of amyloid precursor protein transgenic mice

被引:160
作者
Stalder, AK
Ermini, F
Bondolfi, L
Krenger, W
Burbach, GJ
Deller, T
Coomaraswamy, J
Staufenbiel, M
Landmann, R
Jucker, M
机构
[1] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Cellular Neurol, D-72076 Tubingen, Germany
[2] Univ Basel, Inst Pathol, Dept Neuropathol, CH-4003 Basel, Switzerland
[3] Univ Basel Hosp, Res Dept, CH-4031 Basel, Switzerland
[4] Goethe Univ Frankfurt, Inst Clin Neuroanat, D-60590 Frankfurt, Germany
[5] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland
关键词
Alzheimer; glia; microglia; amyloid; neuroinflammation; GFP; macrophages; transgenic mouse; aging; bone marrow chimera;
D O I
10.1523/JNEUROSCI.2545-05.2005
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:11125 / 11132
页数:8
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