Knockdown of Amyloid Precursor Protein: Biological Consequences and Clinical Opportunities.

Amyloid precursor protein () and its cleavage fragment Amyloid-β (Aβ) have fundamental roles in Alzheimer's disease (AD). Genetic alterations that either increase the overall dosage of or alter its processing to favour the generation of longer, more aggregation prone Aβ species, are directly causative of the disease. People living with one copy of are asymptomatic and reducing has been shown to lower the relative production of aggregation-prone Aβ species . For these reasons, reducing APP expression is an attractive approach for AD treatment and prevention. In this review, we will describe the structure and the known functions of APP and go on to discuss the biological consequences of APP knockdown and knockout in model systems. We highlight progress in therapeutic strategies to reverse AD pathology via reducing expression. We conclude that new technologies that reduce the dosage of expression may allow disease modification and slow clinical progression, delaying or even preventing onset.