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Mean age of onset in familial Alzheimer's disease is determined by amyloid beta 42

2004; Elsevier BV; Volume: 26; Issue: 6 Linguagem: Inglês

10.1016/j.neurobiolaging.2004.08.002

1558-1497

Marco Duering, Marcus O.W. Grimm, Heike S. Grimm, Johannes Schröder, Tobias Hartmann,

Dementia and Cognitive Impairment Research

More than 130 known mutations in the presenilin-1 (PS1) gene result in familial Alzheimer's disease (FAD) with a mutation specific age of disease onset. These mutations increase amyloid beta 42 (A beta42) levels, and this increase has been validated in recent years as one pathogenic factor in FAD. However, further malfunctions of mutant presenilin-1 are discussed as well. In order to assess the weight of A beta42 regarding the pathogenesis of FAD, we expressed mutant forms of PS1 (30-65 years onset age) in COS-7 cells and analyzed amyloid beta levels by a novel ELISA. We found a strong correlation (r = 0.98; p<0.001) between the A beta40/42-ratio and mean age of disease onset indicating a substantial extent of A beta42 contribution to FAD pathology. Our data strongly suggest that A beta42 is the decisive factor for age of onset in FAD.