A FE65 polymorphism associated with risk of developing sporadic late-onsetAlzheimer's disease but not with A beta loading in brains

The FE65 protein was previously described interacting with amyloid protein precursor (APP) and mediating its internalization. Hu et al. (Hum. Genet., 103 (1998) 295) recently reported that a deletion polymorphism in intron 13 of the FE65 gene may be protective for sporadic Alzheimer's disease (AD) f orms and suggested that this deletion may modify splicing between exon 13 a nd 14 (the two exons encoding the interaction domain of FE65 with APP). We tested the im pact of this polymorphism in 646 controls and 639 sporadic AD cases. We were only able to detect a protective effect of the deletion in the population over 75 years (odds ratio = 0.53, 95% confidence interval (0 .35-0.82), P = 0.002). Furthermore, no association of this polymorphism wit h A beta(40), A beta(42(43)) and total A beta loads were detected in 74 AD brains, although, we could expect that this deletion was associated with mo difications of the APP metabolism. in conclusion, the FE65 gene may be a mi nor genetic determinant only for sporadic late-onset AD forms, although, we cannot conclude that this impact is mediated by a modulation of the APP pr ocess and/or A beta peptide deposition. (C) 2000 Elsevier Science Ireland L td. All rights reserved.