Affiliations: [a] Division of Geriatric Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA | [b] GRECC, VA Medical Center, St. Louis, MO, USA | [c] Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
Correspondence:
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Corresponding author: John E. Morley, M.B., B.Ch., Geriatric Medicine, Saint Louis University, School of Medicine, 1402 S. Grand Blvd., M238, St. Louis, MO 63104, USA. E-mail: [email protected].
Abstract: Amyloid-β protein (Aβ) is well recognized as having a significant role in the pathogenesis of Alzheimer's disease (AD). The reason for the presence of Aβ and its physiological role in non-disease states is not clear. In these studies, low doses of Aβ enhanced memory retention in two memory tasks and enhanced acetylecholine production in the hippocampus in vivo. We then tested whether endogenous Aβ has a role in learning and memory in young, cognitively intact mice by blocking endogenous Aβ in healthy 2-month-old CD-1 mice. Blocking Aβ with antibody to Aβ or DFFVG (which blocks Aβ binding) or decreasing Aβ expression with antisense directed at the Aβ precursor, AβPP, all resulted in impaired learning in T-maze foot-shock avoidance. Finally, Aβ1–42 facilitated induction and maintenance of long term potentiation in hippocampal slices, whereas antibodies to Aβ inhibited hippocampal LTP. In conclusion, these results indicate that in normal healthy young animals the presence of Aβ is important for learning and memory.
Keywords: Acetylcholine, amyloid-β, learning, long term potentiation, memory
