Deposition of BACE-1 Protein in the Brains of APP/PS1 Double Transgenic Mice.
The main causes of Alzheimer's disease remain elusive. Previous data have implicated the BACE-1 protein as a central player in the pathogenesis of Alzheimer's disease. However, many inhibitors of BACE-1 have failed during preclinical and clinical trials for AD treatment. Therefore, uncovering the exact role of BACE-1 in AD may have significant impact on the future development of therapeutic agents. Three- and six-month-old female APP/PS1 double transgenic mice were used to study abnormal accumulation of BACE-1 protein in brains of mice here. Immunofluorescence, immunohistochemistry, and western blot were performed to measure the distributing pattern and expression level of BACE-1. We found obvious BACE-1 protein accumulation in 3-month-old APP/PS1 mice, which had increased by the time of 6 months. Coimmunostaining results showed BACE-1 surrounded amyloid plaques in brain sections. The abnormal protein expression might not be attributable to the upregulation of BACE-1 protein, as no significant difference of protein expression was observed between wild-type and APP/PS1 mice. With antibodies against BACE-1 and CD31, we found a high immunoreactive density of BACE-1 protein on the outer layer of brain blood vessels. The aberrant distribution of BACE-1 in APP/PS1 mice suggests BACE-1 may be involved in the microvascular abnormality of AD.
Department of Neurology, First Affiliated Hospital, Henan University, Kaifeng, Henan 475001, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Gang
G
Luo
Department of Neurology, First Affiliated Hospital, Henan University, Kaifeng, Henan 475001, China.
Hongxia
H
Xu
Department of Neurology, First Affiliated Hospital, Henan University, Kaifeng, Henan 475001, China.
Yinuo
Y
Huang
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Dapeng
D
Mo
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Ligang
L
Song
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Baixue
B
Jia
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Bo
B
Wang
Department of Ultrasonic Imaging, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Zhanqiang
Z
Jin
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Zhongrong
Z
Miao
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D050505:Mutant Proteins; C508853:PSEN1 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D053764:Presenilin-1; D011994:Recombinant Proteins; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse