Recent studies on the familial Alzheimer’s disease (FAD)-linked mutations in three independent genes have established the pathogenic role of β-amyloid (Aβ) deposition as a common pathway leading to neurodegeneration. Most of these mutations seem to contribute to Aβ deposition by directly causing the overproduction of Aβ_1–42, a form of Aβ with high insolubility attributed to its carboxyl-terminal structure, through secretory proteolysis. In contrast, the mechanism of Aβ deposition in sporadic Alzheimer’ disease (SAD), which accounts for more than 90% of disease cases, is unclear. Because Aβ overproduction is rarely observed in SAD, a possible candidate mechanism is a decreased degradation, or dyscatabolism, of Aβ. It is notable that a reduction in catabolism of only 30–50% is estimated to exert an equivalent effect on Aβ metabolism as the overproduction seen in FAD. Identification of the in vivo catabolic processes responsible for Aβ disposition would provide a new basis for the development of preventive and therapeutic measures against the disease. I hypothesized recently that aminopeptidase-catalyzed proteolysis of Aβ may limit the rate of Aβ catabolism and that the reduction of a certain aminopeptidase activity would lead to Aβ dyscatabolism and thus to deposition (Aminopeptidase Hypothesis), based on the structural properties of Aβ deposited in human brain. Experimental and clinical observations supporting this hypothesis are accumulating although further work is necessary to fully evaluate its relevance. If the assumption proves to be true, both the familial and sporadic forms of AD may be referred to as “proteolytic disorders” in anabolic and catabolic terms, respectively.