ABNORMAL GEL-ELECTROPHORETIC BEHAVIOR OF PRESENILIN-I AND ITS FRAGMENT

Presenilin 1 (PS-1) is the main causal gene of familial Alzheimer's di sease. In this report, we describe the abnormal behavior of PS-1 in ge l electrophoresis in the presence of SDS. Freshly in vitro synthesized PS-1 was identified as a single molecule with the molecular size of 4 3,000 on SDS gels but was found to disappear after incubation at 37 de grees C for 24 hr due to the formation of aggregates. Intermediate agg regates with Mr 74,000 and 100,000 were formed before the final aggreg ate which was retained at the top of the gel. Thus the amount of 43,00 0-protein species of PS-1 was found to decrease on gels with a concomi tant increase in the amount of 74,000/100,000 proteins. Similar abnorm ality was seen in PS-1 expressed in COS cells transfected with PS-1 cD NA. Moreover, cellular PS-1 was strongly suggested to be cleaved into the fragments with Mr similar to 20,000 in COS and CHO cells. Fragment ation of cellular PS-1 was not affected by the missense point mutation of Ala260Val on PS-1 which was identified in a pedigree with familial Alzheimer's disease. (C) 1996 Academic Press, Inc.