New Insights into Amyloid-β Precursor Protein Specific to Vascular Endothelial Cells

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid beta (Aβ) and phosphorylated tau proteins in the brain. In many AD patients, Aβ accumulates not only in the brain parenchyma but also in cerebral blood vessels, though the molecular mechanisms remain largely unclear. Aβ is generated through the cleavage of amyloid precursor protein (APP) by two enzymes. Recently, our research group has discovered that APP770, an isoform with a different length than that found in the brain parenchyma, is expressed in cerebral blood vessels. This review will first discuss the metabolism and expression of APP, followed by the introduction of a novel AD model mouse that specifically expresses APP770 in vascular endothelium and the newly identified unique glycosylation mechanism of APP770.