Impaired proteolytic processing of presenilin-1 in chromosome 14-linked familial Alzheimer's disease patient lymphocytes.

Many cases of early-onset familial Alzheimer's disease (FAD) are caused by mutations in the presenilin 1 (PS1) and PS2 genes. PS1 protein is generated as a 47 kDa protein and is endoproteolytically cleaved into N-terminal 28 kDa and C-terminal 19 kDa fragments in vivo. To examine whether mutated PS1 protein is abnormally metabolized, we performed immunoblot analysis of lymphoblasts from familial Alzheimer's disease patients and controls. More full-length PS1 was apparently detected in samples from PS1 mutants than those from PS2 mutant and controls. This result suggests that impaired proteolysis of PS1 may be associated with the pathogenesis of FAD. Moreover, our simple test using lymphocytes from FAD patients might be useful from a diagnostic point of view.