Presenilin-1 gene mutations have been proven to be associated with the majority of early-onset familial Alzheimer's disease (FAD). There have been, however, no systematic studies of Presenilin-1 gene mutation in FAD in China so far. We found a novel Val -> Leu missense mutation at codon 97 (Val97Leu) of the Presenilin-1 gene in a Chinese FAD pedigree. To verify whether this mutation is pathologically functional, we established mutation type and wild type Presenilin-1 gene stably transfected cell lines (human neuroblastoma SH-SY5Y cells) to detect beta-amyloid (A beta) concentrations using ELISA and radioimmunity methods. We also examined levels of beta-amyloid precursor protein cleaving enzyme (BACE) and amyloid precursor protein (APP) to explore their impact upon beta-amyloid production. Our results showed that A beta 42 concentration was significantly enhanced at 48 h when compared to that at 24 h in the mutant type cells. At 48 h A beta 42 levels in the V97L mutants was also found to be elevated significantly, both intracellularly and extracellularly when compared to wild and mock transfected cells. The total A beta in either group did not alter, consistent with unchanged BACE and APP expression levels. Our data reveal that the Presenilin-1 V97L variant can elevate A beta 42 levels both intracellularly and extracellularly, and was a potentially pathogenic mutation for this Chinese FAD pedigree. It also suggests that there are common mechanisms in the pathogenesis of FAD between Chinese and other ethnic populations, although their gene mutation sites are different. (c) 2006 Published by Elsevier Ireland Ltd.