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(American Journal of Pathology. 2000;157:895-904.)
© 2000 American Society for Investigative Pathology

Regular Articles

Expression of Macrophage Colony-Stimulating Factor Receptor Is Increased in the AßPP^V717F Transgenic Mouse Model of Alzheimer’s Disease

Greer M. Murphy, Jr.^*, Feifei Zhao^*, Lan Yang^* and Barbara Cordell

From the Department of Psychiatry and Behavioral Sciences,^*
Stanford University School of Medicine, Stanford; and Scios, Inc.,
Sunnyvale, California

Inflammation is an important neuropathological change in Alzheimer’s disease (AD). However, the pathophysiological factors that initiate and maintain the inflammatory response in AD are unknown. We examined AßPP^V717F transgenic mice, which show numerous brain amyloid-ß (Aß) deposits, for expression of the macrophage colony-stimulating factor (M-CSF) and its receptor (M-CSFR). M-CSF is increased in the brain in AD and dramatically augments the effects of Aß on cultured microglia. AßPP^V717F animals 12 months of age showed large numbers of microglia strongly labeled with an M-CSFR antibody near Aß deposits. M-CSFR mRNA and protein levels were also increased in brain homogenates from AßPP^V717F animals. Dystrophic neurites and astroglia showed no M-CSFR labeling in the transgenic animals. A M-CSF antibody decorated neuritic structures near hippocampal Aß deposits in transgenic animals. M-CSF mRNA was also increased in AßPP^V717F animals in comparison with wild-type controls. Simultaneous overexpression of M-CSFR and its ligand in AßPP^V717F animals could result in augmentation of Aß-induced activation of microglia. Because chronic activation of microglia is thought to result in neuronal injury, the M-CSF system may be a potential target for therapeutic intervention in AD.

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