huAPP-Aβ Mouse

The APP gene encodes the Amyloid Precursor Protein, a type I transmembrane glycoprotein that is ubiquitously expressed but reaches its highest levels in the central nervous system, particularly in the cerebral cortex and hippocampus. Following translation, the APP protein is proteolytically processed via two primary pathways: the non-amyloidogenic pathway, which prevents Aβ formation, and the amyloidogenic pathway, where sequential cleavage by β-secretase (BACE1) and γ-secretase releases amyloid-beta (Aβ) peptides ^[1]. While its precise physiological role remains an area of active research, APP is known to function in synaptic formation and repair, anterograde neuronal transport, and cell-to-cell adhesion ^[2]. Pathological mutations or duplications of the APP gene are primary drivers of Alzheimer’s Disease (AD) and Cerebral Amyloid Angiopathy (CAA), characterized by the extracellular accumulation of Aβ plaques and vascular deposits that lead to neurodegeneration and cognitive decline ^[3].

The huAPP-Aβ mouse is a humanized model constructed via gene editing. The sequences from upstream of exon 16 to downstream of exon 17 of the mouse App were replaced with the sequences from upstream of exon 16 to downstream of exon 17 of the human APP. This model is suitable for studying neurodegenerative diseases such as Alzheimer's disease (AD), as well as for the research, development, and efficacy evaluation of AD therapeutic strategies targeting APP.