APP mRNA (RNAi)

Class

Amyloid precursor protein (APP)-lowering RNAi therapeutic

Amyloid precursor protein (APP) is a transmembrane protein expressed throughout the nervous system. Enzymes called secretases cleave it sequentially to produce several fragments, including amyloid-beta peptides that aggregate into the plaques characteristic of Alzheimer's disease and that also deposit in blood vessel walls in cerebral amyloid angiopathy. RNA interference (RNAi) therapeutics directed at APP messenger RNA (mRNA) work upstream of this process: rather than clearing amyloid plaques after they form or blocking the secretase enzymes that cut APP, they reduce the amount of APP protein made in the first place, lowering the substrate available for amyloid-beta generation. This is a distinct strategy from antibody-based plaque clearance or secretase inhibition, aiming for a sustained reduction in amyloid production at its source. Because APP and its cleavage fragments also participate in normal neuronal signaling, growth, and injury response, broadly lowering APP carries theoretical trade-offs alongside its intended benefit. This mechanism is studied mainly in the context of Alzheimer's disease and cerebral amyloid angiopathy, disorders in which excess amyloid-beta production and vascular or parenchymal deposition are thought to drive progressive neuronal and vascular damage.