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. 2009 Mar 20;452(3):277-80.
doi: 10.1016/j.neulet.2009.01.071. Epub 2009 Feb 4.

Expression and localization of lactotransferrin messenger RNA in the cortex of Alzheimer's disease

Li An  1 , Haruhisha Sato, Yoshihiro Konishi, Douglas G Walker, Thomas G Beach, Joseph Rogers, Ikuo Tooyama
Affiliations

Expression and localization of lactotransferrin messenger RNA in the cortex of Alzheimer's disease

Li An et al. Neurosci Lett. .

Abstract

We and others have previously reported that lactotransferrin (LF), acting both as an iron-binding protein and inflammatory modulator, is greatly up-regulated in the brain of patients with Alzheimer's disease (AD). However, it remains unknown which type of cells express LF in the brain of AD. In this study, therefore, we investigated the expression and localization of LF messenger RNA (mRNA) in the cerebral cortex of AD and control cases using real-time polymerase chain reaction (PCR) and in situ hybridization histochemistry. Real-time PCR demonstrated that LF mRNA expression in the cortex of AD cases was significantly greater than that in control cases. LF mRNA-positive granules were observed in the cortex by in situ hybridization histochemistry, and the number of positive granules was increased in AD cases compared to controls. The double staining technique of LF mRNA in situ hybridisation and D-related human leukocyte antigen (HLA-DR) immunohistochemistry revealed that positive granules were localized in a subpopulation of HLA-DR-positive reactive microglia. In addition, LF mRNA-positive granules were observed in some cells that were negative for HLA-DR. These cells were also negative for CD4 and CD8 but positive for leukocyte common antigen (CD45RB), suggesting they were monocytes/macrophages. These results indicate that reactive microglia in the cerebral cortex and monocytes/macrophages infiltrating from the circulation might be responsible for synthesizing LF in AD brain.

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Figures

Figure 1
Figure 1
Lactotransferrin (LF) mRNA expression levels in the cerebral cortex of control and Alzheimer’s disease (AD) patients. Asterisk indicates significantly different to control (p < 0.05).
Figure 2
Figure 2
In situ hybridization histochemistry of the cerebral cortex of control (A, B, C) and Alzheimer’s disease (AD) cases (D, E, F) using antisense (A, B, D, E) and sense (C, F) probes. Granules imply the localization of lactotransferrin mRNA. The number of positive granules is increased in AD cases (D) compared to controls (A). Using sense probes (C and F) as the control for the antisense probe, no granule of blue color is detected in the cortex. Bars = 100 μm in A, C, D, F, and 50 μm in B, E.
Figure 3
Figure 3
Double staining of lactotransferrin (LF) mRNA in situ hybridization and D-related human leukocyte antigen (HLA-DR) immunohistochemistry in the cerebral cortex of an Alzheimer’s disease case. LF mRNA is expressed in a subpopulation of HLA-DR-positive reactive microglia (black arrows in A and B). Some LF mRNA-positive cells which are negative for HLA-DR are seen in the parenchyma of the cerebral cortex (red arrow in B) and in the vicinity of microvessels (red arrow in C). Bars = 50 μm.
Figure 4
Figure 4
Double staining of lactotransferrin (LF) mRNA in situ hybridization and CD4 (A), CD8 (B) or leukocyte common antigen (LCA) immunohistochemistry (C) in the cerebral cortex of an Alzheimer’s disease case. LF-positive signals (arrows in A and B) were negative for CD4 (arrowheads in A) and CD8 (arrowheads in B). Granular signals for LF mRNA are seen in the cytoplasm of LCA-positive cells (arrows in C). Bar = 50 μm.
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