Chapter 6 - Post-translational control of the amyloid β-protein precursor processing

Abstract

This chapter discusses posttranslational control of the amyloid β-protein precursor (APP) processing. APP processing appears to be under complex regulation. This regulation is apparently important under both normal and pathological conditions. The observation that Aβ formation can be regulated by various means is of direct clinical interest. This raises the possibility that altered APP processing may cause an increase in Aβ formation in Alzheimer's disease (AD), and suggests that it may be possible to regulate the production of Aβ as a therapeutic approach in AD. By studying APP processing in areas of nerve terminal degeneration, far from the lesion site, it could be shown that the changes in APP processing are caused by neuronal degeneration affecting APP processing, rather than altered APP processing affecting neuronal degeneration. It is found even in individuals where increased Aβ formation is not the cause of AD but some other cause, such as the presence of ApoE4, which causes AI3 accumulation and hence synaptic loss, decreasing Aβ formation may be beneficial. The observation that lithium treatment alters APPs levels in cerebrospinal fluid of patients supports regulating APP processing as a therapeutic approach in AD.