The beta-amyloid precursor protein and its derivatives: from biology to learning and memory processes.
Intensive investigation towards the understanding of the biology and physiological functions of the beta-amyloid precursor protein (APP) have been supported since it is known that a 39-43 amino acid fragment of APP, called the beta-amyloid protein (Abeta), accumulates in the brain parenchyma to form the typical lesions associated with Alzheimer's disease (AD). It emerges from extensive data that APP and its derivatives show a wide range of contrasting physiological properties and therefore might be involved in distinct physiological functions. Abeta has been shown to disrupt neuronal activity and to demonstrate neurotoxic properties in a wide range of experimental procedures. In contrast, both in vitro and in vivo studies suggest that APP and/or its secreted forms are important factors involved in the viability, growth and morphological and functional plasticity of nerve cells. Furthermore, several recent studies suggest that APP and its derivatives have an important role in learning and memory processes. Memory impairments can be induced in animals by intracerebral treatment with Abeta. Altered expression of the APP gene in aged animals or in genetically-modified animals also leads to memory deficits. By contrast, secreted forms of APP have recently been shown to facilitate learning and memory processes in mice. These interesting findings open novel perspectives to understand the involvement of APP in the development of cognitive deficits associated with AD. In this review, we summarize the current data concerning the biology and the behavioral effects of APP and its derivatives which may be relevant to the roles of these proteins in memory and in AD pathology.
Dodart
J C
JC
Laboratoire d'Ethologie et Neurobiologie, URA-CNRS 1295, ULP, Strasbourg, France. jcdodart@currif.u-strasbg.fr
Mathis
C
C
Ungerer
A
A
D000544:Alzheimer Disease / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000031:analogs & derivatives* / Q000502:physiology*; D000818:Animals; D003072:Cognition Disorders / Q000503:physiopathology; D006801:Humans; D007858:Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor