How Does N- and O-Glycosylation Affect the Formation and Accumulation of Amyloid β-Peptide?

Abstract

Deposition of amyloid β (Aβ) in the brain is closely associated with Alzheimer’s disease (AD). Aβ is generated from β-amyloid precursor protein (APP) by the actions of β-and γ-secretases. APP and APP-cleaving enzymes (secretases) are membrane-bound glycoproteins. Several recent reports have shown that glycosylation deficiency causes abnormalities of the functional glycoprotein through protein instability, conformation changes, and impaired localization. Indeed, several reports have suggested that particular glycosylation changes would affect the functionality of APP or secretases to modulate Aβ production. In this review, I first describe the expression pattern, metabolic pathway, and posttranslational modification of APP, and then summarize recent studies, including ours, showing that particular glycosylation changes affect the formation, accumulation, and clearance of Aβ.