The physiological role of the amyloid precursor protein as an adhesion molecule in the developing nervous system

Abstract

The amyloid precursor protein (APP) is a type I transmembrane glycoprotein better known for its participation in the physiopathology of Alzheimer disease as the source of the beta amyloid fragment. However, the physiological functions of the full length protein and its proteolytic fragments have remained elusive. APP was first described as a cell-surface receptor; nevertheless, increasing evidence highlighted APP as a cell adhesion molecule. In this review, we will focus on the current knowledge of the physiological role of APP as a cell adhesion molecule and its involvement in key events of neuronal development, such as migration, neurite outgrowth, growth cone pathfinding, and synaptogenesis. Finally, since APP is over-expressed in Down syndrome individuals because of the extra copy of chromosome 21, in the last section of the review, we discuss the potential contribution of APP to the neuronal and synaptic defects described in this genetic condition. This Review followed a CAEN Return Home grant.

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“…The enrichment of APP in these highly motile subdomains suggests that APP plays a role as a particularly ‘plastic’ CAM (Sosa et al . ).…”

“…As detailed here (Sosa et al . ), APP displays several notable CAM‐like features. The large extracellular domain of APP can self‐dimerize as well as interact with numerous extracellular matrix molecules (ECM) and other neuronal CAMs.…”

“…The current review (Sosa et al . ) provides a compelling model of APP functions, based on diverse research across many groups, concluding that APP acts as a cell adhesion molecule (CAM) in the central nervous system regulating neuronal migration, axonal outgrowth, and synaptogenesis.…”

“…However, great gains have been made in AD research since then despite the lack of consensus regarding the physiological roles of APP. The current review (Sosa et al 2017) provides a compelling model of APP functions, based on diverse research across many groups, concluding that APP acts as a cell adhesion molecule (CAM) in the central nervous system regulating neuronal migration, axonal outgrowth, and synaptogenesis.…”

“…APP is found both pre-and post-synaptically, and its extracellular domains interact with a wide variety of molecules important to synapse stability. The enrichment of APP in these highly motile subdomains suggests that APP plays a role as a particularly 'plastic' CAM (Sosa et al 2017).…”