Upregulation of BACE1 and beta-amyloid protein mediated by chronic cerebral hypoperfusion contributes to cognitive impairment and pathogenesis of Alzheimer's disease.
Chronic cerebral hypoperfusion (CCH) increases the risk of Alzheimer disease (AD) through several biologically plausible pathways, but the relationship between CCH and the development of AD remains uncertain. To investigate expression of APP, BACE1 and A beta in the hippocampus of BCCAO rats and study pathophysiological mechanism of AD from CCH. CCH rat model was established by chronic bilateral common carotid artery occlusion (BCCAO). Behavior was evaluated after BCCAO with Morris water maze and open-field task. Expression of A beta was measured by enzyme linked immunosorbent assay (ELISA). beta-Amyloid precursor protein cleavage enzyme 1 (BACE1) and beta-amyloid precursor protein (APP) were tested by ELISA, Western blotting and RT-PCR. Cognitive impairment occurred with CCH by Morris water maze test and open-field task. The BACE1 and A beta level in BCCAO rats was more increased than sham-operation control rats (P < 0.01) but APP had no difference(P > 0.05). The expression of BACE1 and A beta has no inter-group difference in BCCAO rats (P > 0.05). The level of BACE1 and A beta had positive correlation with cognitive impairment (P < 0.01) while no correlation was observed between APP and cognitive impairment. Chronic cerebral ischemia contributes to cognitive impairment and vascular pathogenesis of Alzheimer's disease that chronic cerebral hypoperfusion increases BACE1 and A beta level in brain.
Zhiyou
Cai
C
Chongqing Key Laboratory of Neurology, Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Youyi Road, Yuzhong, 400016, Chongqing, China. czy000806@163.com
Yong
Yan
Y
Shanquan
Sun
S
Jun
Zhang
Z
Liangguo
Huang
H
Ling
Yan
Y
Jieying
Li
L
D000544:Alzheimer Disease / Q000209:etiology*; D053829:Amyloid Precursor Protein Secretases / Q000096:biosynthesis*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis*; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology*; D003072:Cognition Disorders / Q000209:etiology*; D004797:Enzyme-Linked Immunosorbent Assay; D004924:Escape Reaction / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D010446:Peptide Fragments / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat