Deposition of lactoferrin in fibrillar-type senile plaques in the brains of transgenic mouse models of Alzheimer's disease.
We and others have previously reported that lactoferrin (LF), which acts as both an iron-binding protein and an inflammatory modulator, is strongly up-regulated in the brains of patients with Alzheimer's disease (AD). We have also studied the expression and localization of LF mRNA in the brain cortices of patients with AD. In this study, we investigated immunohistochemically the localization of LF in the brains of APP-transgenic mice, representing a model of AD. No LF immunoreactivity was detected in the brains of the wild-type mice. In the transgenic AD mice, LF deposition was detected in the brains. Double-immunofluorescence staining with antibodies directed against the amyloid-beta peptide (Abeta) and LF localized the LF depositions to amyloid deposits (senile plaques) and regions of amyloid angiopathy. Senile plaque formation precedes LF deposition in AD. In the transgenic mice aged <18 months, most of senile plaques were negative for LF. LF deposits appeared weakly at about 18 months of age in these mice. Both the intensity and number of LF-positive depositions in the transgenic mice increased with age. Double-staining for LF and thioflavin-S revealed that LF accumulated in thioflavin-S-positive, fibrillar-type senile plaques. The up-regulation of LF in the brains of both AD patients and the transgenic mouse model of AD provides evidence of an important role for LF in AD-affected brain tissues.
Wang
Ligang
L
Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu 520-2192, Japan.
Sato
Haruhisa
H
Zhao
Shiguang
S
Tooyama
Ikuo
I
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007781:Lactoferrin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology
D016564:Amyloid beta-Protein Precursor; D007781:Lactoferrin