Beta-site APP cleaving enzyme 1 (BACE1) is increased in remaining neurons in Alzheimer's disease brains.
Alzheimer's disease (AD) is characterized by the extensive deposition of amyloid beta protein (Abeta) in the brain cortex. Abeta is produced from beta-amyloid precursor protein (APP) by beta-secretase and gamma-secretase. beta-Secretase has been identified as beta-site APP cleaving enzyme1 (BACE1). We produced rabbit polyclonal antibodies against the amino and the carboxyl terminals of BACE1. Using these antibodies, BACE1 was characterized in temporal lobe cortices by Western blotting and immunohistochemistry. Immunohistochemical studies employing anti-GFAP and anti-MAP2 antibodies as well as anti-BACE1 antibodies showed that BACE1 was expressed exclusively in neurons but not in glial cells. Brain samples were directly extracted by 0.5% SDS and analyzed by Western blotting and densitometer. Although the mean level of BACE1/mg protein in AD brains was not increased, the ratio of BACE1 to MAP2 or to NSE was significantly increased compared with that in control brains. Taken together, these findings suggest that those neurons that survive in AD brains might generate more BACE1 than normal neurons in control brains, indicating that increased BACE1 activity could be one of the causes of AD. This could justify the development of anti-BACE1 drugs for AD treatment.
Harada
Hirotsugu
H
Department of Neurology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. haradah@nona.dti.ne.jp
Tamaoka
Akira
A
Ishii
Kazuhiro
K
Shoji
Shin'ichi
S
Kametaka
Satoshi
S
Kametani
Fuyuki
F
Saito
Yuko
Y
Murayama
Shigeo
S
D000544:Alzheimer Disease / Q000201:enzymology*; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology*; D010450:Endopeptidases / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D009474:Neurons / Q000201:enzymology*; D010751:Phosphopyruvate Hydratase / Q000096:biosynthesis
D005904:Glial Fibrillary Acidic Protein; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D010751:Phosphopyruvate Hydratase