Is the presenilin-1 E318G missense mutation a risk factor for Alzheimer's disease?

Nearly all of the presenilin-1 (PSEN-1) mutations are missense mutations le ading to Alzheimer's disease (AD). The role of the mutation E318G (a substi tution of glutamic acid to glycine) in the PSEN-1 is controversial. It has been found both in AD patients and in non-demented control individuals. Usi ng the polymerase chain reaction and the restriction fragment length polymo rphism method, we screened for E318G mutation in a total of 16 familial (FA D) cases, in 64 sporadic neuropathologically confirmed AD cases and in 270 non-demented controls including 35 neuropathologically confirmed individual s. We detected the E318G mutation in four FAD cases, seven sporadic AD case s and 10 control individuals with highly varying onset-ages. Odds rations f or carrying the mutation were 7.6 and 3 in FAD and sporadic AD cases, respe ctively. Our results suggest that this mutation could be a risk factor in t he Finnish FAD and sporadic AD population. It may be in linkage disequilibr ium with a pathogenic change somewhere else in the PSEN-1 gene or in close proximity to the PSEN-1 gene. (C) 2000 Elsevier Science Ireland Ltd. All ri ghts reserved.