Cleavage of amyloid precursor protein elicited by chronic cerebral hypoperfusion.
In the present study, we sought to determine whether low-grade, chronic vascular insufficiency induced in a rodent model of chronic cerebrohypoperfusion is sufficient, in and of itself, to trigger cleavage of the amyloid precursor protein (APP) into beta A-sized fragments. We report that chronic two vessel occlusion (2VO) results in progressive accumulation of beta A peptides detected by Western analysis in aged rats correlating with a shift in the immunohistochemical localization of APP from neurons to extracellular deposits in brain parenchyma. These data indicate that the 2VO paradigm reproduces features of beta A biogenesis characteristic of sporadic Alzheimer's disease.
Bennett
S A
SA
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, KIH 8M5, Ottawa, ON, Canada. bennett@aix1.uottawa.ca
Pappas
B A
BA
Stevens
W D
WD
Davidson
C M
CM
Fortin
T
T
Chen
J
J
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism*; D017536:Carotid Artery, Common / Q000502:physiology; D002908:Chronic Disease; D005110:Extracellular Space / Q000378:metabolism; D007150:Immunohistochemistry; D008026:Ligation; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley
D016564:Amyloid beta-Protein Precursor