Alzheimer's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Alzheimer's Disease, including details on diagnosis, memory loss, heredity, treatment, medication.

Presenilin-1 mutation E318G and familial Alzheimer's disease in the Italian population.

Albani D, Roiter I, Artuso V, Batelli S, Prato F, Pesaresi M, Galimberti D, Scarpini E, Bruni A, Franceschi M, Piras MR, Confaloni A, Forloni G

Department of Neuroscience, Mario Negri Institute for Pharmacological Research, via Eritrea 62, 20157 Milan, Italy. albani@marionegri.it

Presenilin-1 (PSEN-1) is a component of the gamma-secretase complex involved in beta-amyloid precursor protein (betaAPP) processing. To date about 140 pathogenic mutations in the PSEN-1 gene have been identified and their main biochemical effect is to increase the production of the fibrillogenic peptide Abeta(1-42). An exception is the PSEN-1 [E318G] mutation that does not alter Abeta(1-42) generation and is generally considered a non-pathogenic polymorphism. Nevertheless, this mutation was reported to be a genetic risk factor for familial Alzheimer's disease (FAD) in the Australian population. To independently confirm this indication, we performed a case-control association study in the Italian population. We found a significant association (p<0.05, Fisher's exact test) between the presence of PSEN-1 [E318G] and FAD. In addition, on measuring the Abeta(1-42) and Abeta(1-40) concentrations in fibroblast-conditioned media cultured from PSEN-1 [E318G] carriers and PSEN-1 [wild type] controls we noted a significant decrease (p<0.05, Mann-Whitney test) in the Abeta(1-42)/Abeta(1-40) ratio in PSEN-1 [E318G] carriers, suggesting a peculiar biochemical effect of this mutation.

Published 23 October 2007 in Neurobiol Aging, 28(11): 1682-8.
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