Amyloid-β As a biologically active peptide in CNS

Abstract

Over the last decade, amyloid-P (AP), which is detected in both cerebrospinal fluid and plasma in healthy individuals throughout life (Seubert et al., 1992), has been a focus of considerable research. It has attracted attention as a peptide that plays pivotal role in the onset of Alzheimer's disease (AD) (Hardy and Selkoe, 2002) as well as a physiologically relevant messenger in CNS (Kamenetz et al., 2003; Plant et al., 2003). Recent observations indicate that nicotinic acetylcholine receptors (nAChRs) act as receptors for Aβ (Wang et al., 2000b; Wang et al., 2000a). Here we briefly review electrophysiological data concerning Aβ effects that are relevant for AD as well as normal physiology of CNS. We present data obtained in our laboratory comparing the effects of Aβ and the nAChR antagonist, mecamylamine, on long-term synaptic plasticity in hippocampal dentate gyms (DG), and propose a hypothesis concerning an interaction between nAChRs and Aβ in synaptic transmission and long-term synaptic plasticity as well as AD pathogenesis.