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

https://doi.org/10.1016/S0304-3940(99)00891-5Get rights and content

Abstract

Nearly all of the presenilin-1 (PSEN-1) mutations are missense mutations leading to Alzheimer's disease (AD). The role of the mutation E318G (a substitution 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. Using the polymerase chain reaction and the restriction fragment length polymorphism method, we screened for E318G mutation in a total of 16 familial (FAD) cases, in 64 sporadic neuropathologically confirmed AD cases and in 270 non-demented controls including 35 neuropathologically confirmed individuals. We detected the E318G mutation in four FAD cases, seven sporadic AD cases and 10 control individuals with highly varying onset-ages. Odds rations for carrying the mutation were 7.6 and 3 in FAD and sporadic AD cases, respectively. Our results suggest that this mutation could be a risk factor in the Finnish FAD and sporadic AD population. It may be in linkage disequilibrium with a pathogenic change somewhere else in the PSEN-1 gene or in close proximity to the PSEN-1 gene.

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Acknowledgements

The authors thank Ms. Marjo Heikkinen and Ms. Leila Antikainen for their skilful technical help. The study was supported by a grant from the Health Research Council of the Academy of Finland and EVO grant 5032 of Kuopio University Hospital.

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