– Amyloid precursor protein (APP) is a type I membrane protein with several isoforms due to alternative splicing, performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Of the three major splice isoforms of APP (APP695, APP751, and APP770) APP695 is the predominant neuronal form from which Amyloid beta peptide and transcriptionally-active cleaved intracellular domain of APP (AICD) are preferentially generated by selective processing through the amyloidogenic pathway. Human APP695 consists of a 17 amino acid (aa) signal sequence, a 607 aa extracellular domain (ECD), a 24 aa transmembrane domain, and a 47 aa cytoplasmic domain. Within the ECD, human APP695 shares 97% aa sequence identity with mouse and rat APP695. Amyloid beta is a major molecule implicated in pathogenesis of Alzheimer’s disease (AD) and related dementias. AICD regulates expression by direct promoter binding of multiple genes, including APP itself, the beta-secretase, BACE-1 and the Amyloid beta-degrading enzyme, Neprilysin. As such, APP695 plays an important role in brain development, learning and memory, synaptic plasticity, and neurodegeneration including AD.