TREM2 is upregulated in amyloid plaque‐associated microglia in aged APP23 transgenic mice

GLIA - Tập 56 Số 13 - Trang 1438-1447 - 2008
Stefanie Frank1,2, Guido J. Burbach1,2, Michael Bonin3, Michael Walter3, Wolfgang J. Streit4, Ingo Bechmann1, Thomas Deller1
1Institute of Clinical Neuroanatomy, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, Frankfurt am Main, Germany
2these authors contributed equally to this work
3Department of Medical Genetics, Eberhard Karls-University, Tübingen, Germany
4Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida

Tóm tắt

AbstractAlzheimer's disease (AD) is characterized by extracellular deposits of amyloid‐β protein which attract dense clusters of microglial cells. Here, we analyzed amyloid plaque‐associated areas in aged APP23 transgenic mice, an animal model of AD, by combining laser microdissection with microarray analysis and quantitative RT‐PCR (qPCR). By comparing gene expression profiles, we found that 538 genes (1.3% of a total of 41,234 analyzed genes) were differentially expressed in plaque‐associated versus plaque‐free tissue of aged APP23 transgenic mice. One of these genes is the microglia‐associated triggering receptor expressed on myeloid cells (TREM2) which enhances phagocytosis, but abrogates cytokine production as well as TLR and Fc receptor‐mediated induction of TNF secretion. Western Blot analysis demonstrated an upregulation of TREM2 protein in APP23 transgenic compared with nontransgenic mice. Confocal imaging studies, furthermore, confirmed colocalization of TREM2 protein with microglia. Thus, when TREM2 is induced on microglia in plaque‐loaded brain areas the respective signaling may prevent inflammation‐induced bystander damage of neurons. At the same time, TREM2 signaling may also account for the failure to sufficiently eliminate extracellular amyloid with the help of a systemic immune response. © 2008 Wiley‐Liss, Inc.

Từ khóa


Tài liệu tham khảo

10.1159/000213842

10.1016/S0197-4580(00)00124-X

10.1385/NMM:7:3:217

10.1016/j.it.2006.11.007

10.1016/S0197-0186(01)00045-6

10.1016/S0006-8993(02)02504-0

10.1007/BF00308809

10.1007/978-3-7091-6467-9_11

10.1016/S0165-0270(03)00232-2

10.1002/glia.20057

10.1016/j.jneumeth.2004.03.022

10.1016/j.neurobiolaging.2005.12.003

10.1038/nri1106

10.1186/1742-2094-3-27

10.1186/1471-2164-6-59

10.1038/nn1472

10.4049/jimmunol.171.2.594

10.1002/glia.10146

10.1126/science.274.5289.998

10.1016/j.neulet.2006.10.029

10.1016/j.it.2006.11.004

10.4049/jimmunol.177.4.2051

10.1016/j.brainresrev.2004.12.012

10.1097/00002093-200401000-00008

10.1006/bbrc.1998.8120

10.1007/BF00227737

10.1523/JNEUROSCI.23-09-03607.2003

10.1016/j.nbd.2004.09.007

10.1016/S1525-1578(10)60009-8

10.1016/j.tins.2004.06.007

10.1016/S1471-4906(01)02063-4

10.1038/4806

McClintick JN, 2003, Reproducibility of oligonucleotide arrays using small samples, BMC Genomics, 4, 4, 10.1186/1471-2164-4-4

10.1002/glia.440070114

10.1016/j.neuint.2006.04.002

10.1016/j.jneuroim.2006.11.032

10.1073/pnas.0609377104

10.1126/science.1110647

10.1126/science.1078259

10.1002/eji.200636837

10.1038/nm1653

10.1002/glia.10153

10.1046/j.1471-4159.2002.01243.x

10.1186/1471-2199-7-3

10.1111/j.1460-9568.2004.03729.x

10.1172/JCI31450

10.1016/j.neuron.2006.01.022

10.1016/S0165-5728(02)00112-1

10.1038/sj.mp.4000397

10.1016/S0002-9440(10)65423-5

10.1016/j.brainresrev.2004.12.013

10.1016/j.tins.2006.07.001

10.1179/016164105X49463a

10.1186/1742-2094-1-14

10.1073/pnas.94.24.13287

10.1515/REVNEURO.1999.10.1.15

10.1111/j.1749-6632.2000.tb06915.x

10.1371/journal.pmed.0040124

10.1084/jem.20041611

10.1002/eji.200425932

10.1093/jnen/60.9.885

10.4049/jimmunol.177.6.3520