A physiological role for amyloid-beta protein:enhancement of learning and memory.
Amyloid-beta protein (Abeta) is well recognized as having a significant role in the pathogenesis of Alzheimer's disease (AD). The reason for the presence of Abeta and its physiological role in non-disease states is not clear. In these studies, low doses of Abeta enhanced memory retention in two memory tasks and enhanced acetylecholine production in the hippocampus in vivo. We then tested whether endogenous Abeta has a role in learning and memory in young, cognitively intact mice by blocking endogenous Abeta in healthy 2-month-old CD-1 mice. Blocking Abeta with antibody to Abeta or DFFVG (which blocks Abeta binding) or decreasing Abeta expression with antisense directed at the Abeta precursor, AbetaPP, all resulted in impaired learning in T-maze foot-shock avoidance. Finally, Abeta 1-42 facilitated induction and maintenance of long term potentiation in hippocampal slices, whereas antibodies to Abeta inhibited hippocampal LTP. In conclusion, these results indicate that in normal healthy young animals the presence of Abeta is important for learning and memory.
Morley
John E
JE
Division of Geriatric Medicine, Saint Louis University School of Medicine, St Louis, Missouri 63104, USA.
Farr
Susan A
SA
Banks
William A
WA
Johnson
Steven N
SN
Yamada
Kelvin A
KA
Xu
Lin
L
D000109:Acetylcholine / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D055664:Electrochemical Techniques / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D017551:Microdialysis / Q000379:methods; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D016229:Amyloid beta-Peptides; D000906:Antibodies; D010446:Peptide Fragments; D010455:Peptides; C075222:amyloid beta-protein (1-42); C092395:amyloid beta-protein (12-28); D000109:Acetylcholine