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.

For the accurate biosynthesis of glycans, not only the expression levels of the enzymes but also the transport of lipids and proteins, which are substrates for glycosylation, and the biosynthetic enzyme itself must be correctly regulated. Genome-wide search for cellular factors using CRISPR gene knockout libraries is a useful method to elucidate this regulatory mechanism. In particular, since some bacterial toxins and viruses utilize glycans as receptors, a host cell factor search against these pathogens can comprehensively identify factors that affect glycan biosynthesis. This review outlines factors related to glycan biosynthesis that have been isolated in our group’s screening against bacterial toxins and viruses.

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.

For the accurate biosynthesis of glycans, not only the expression levels of the enzymes but also the transport of lipids and proteins, which are substrates for glycosylation, and the biosynthetic enzyme itself must be correctly regulated. Genome-wide search for cellular factors using CRISPR gene knockout libraries is a useful method to elucidate this regulatory mechanism. In particular, since some bacterial toxins and viruses utilize glycans as receptors, a host cell factor search against these pathogens can comprehensively identify factors that affect glycan biosynthesis. This review outlines factors related to glycan biosynthesis that have been isolated in our group’s screening against bacterial toxins and viruses.