Oligomers of the amyloid-beta protein disrupt working memory: confirmation with two behavioral procedures.
Converging lines of evidence suggest that oligomers of amyloid-beta play a role in the cognitive impairment characteristic of Alzheimer's disease, but only three studies have provided experimental evidence of such impairment. To provide additional information about the effects of these oligomers on memory, the present study examined the memory of groups of rats exposed to ICV injections of the culture media (CM) of Chinese Hamster Ovary cells that were (7PA2) and were not (CHO-) transfected with a human mutation of amyloid precursor protein that appears to cause early-onset Alzheimer's disease. The 7PA2 CM, which contained concentrations of soluble amyloid-beta oligomers physiologically relevant to those found in human brain, significantly disrupted working memory in rats tested in a radial-arm maze. In contrast, CHO- CM, which did not contain such oligomers, had no effect on memory. The disruptive effects of 7PA2-derived amyloid-beta oligomers, evident 2h after exposure, disappeared within a day. These findings are compared to results from 7PA2 CM tested under a complex procedure thought to measure aspects of executive function. The results confirm the disruptive effects of low-n amyloid-beta oligomers and extend them to a well-established rat model of memory.
Poling
Alan
A
Department of Psychology, Western Michigan University, Kalamazoo, MI 49008, USA. alan.poling@wmich.edu
Morgan-Paisley
Kineta
K
Panos
John J
JJ
Kim
Eun-Mee
EM
O'Hare
Eugene
E
Cleary
James P
JP
Lesné
Sylvain
S
Ashe
Karen H
KH
Porritt
Matthew
M
Baker
Lisa E
LE
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000633:toxicity; D005260:Female; D006801:Humans; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D008970:Molecular Weight; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D017077:Culture Media, Conditioned; D010446:Peptide Fragments