Eleven early-onset dementia families, all with affected individuals who have either presented clinical symptoms of early onset familial Alzheimer's disease (EOFAD) or have been confirmed to have EOFAD by autopsy, and two early onset cases with biopsy-confirmed AD pathology, were screened for missense mutations in the entire coding region of presenilin-1 (PS-1) and -2 (PS-2) genes.
These results suggest (i) that, in contrast to mutations in PS-1, mutations in PS-2 are a relatively rare cause of FAD; (ii) that other genetic or environmental factor modify the AD phenotype associated with PS-2 mutations; and (iii) that still other FAD susceptibility genes remain to be identified.