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O4‐01‐02: APP and BACE1 miRNA genetic variability in risk for Alzheimer's disease
Author(s) -
Bettens Karolien,
Brouwers Nathalie,
Van Miegroet Helen,
Engelborghs Sebastiaan,
De Deyn Peter,
Theuns Jessie,
Sleegers Kristel,
Van Broeckhoven Christine
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.05.514
Subject(s) - microrna , gene , genetics , untranslated region , biology , three prime untranslated region , in silico , allele , single nucleotide polymorphism , alzheimer's disease , disease , computational biology , messenger rna , medicine , genotype , pathology
developed cognitive problems at the age of 75 years. A brother, currently aged 53 years, was also shown to carry the mutation but does not show signs of dementia. Genotyping of control individuals showed that the mutation was absent from 940 chromosomes. The mutated amino acid residue is evolutionary conserved and flanks the alternative b-secretase processing site (b’-site). Proteolytic cleavage at this site generates N-terminally truncated Ab peptides starting at position 11. We are currently examining whether the p.E682 K mutation is affecting the b’-secretase processing of APP. Conclusions: We identified a novel APP mutation p.E682 K in exon 16 of APP in a familial early-onset AD patient which we nicknamed Leuven APP mutation. Also, p.E682 K is the first mutation identified at the b’-site supporting a role for codon 11 N-truncated Ab peptides in AD pathogenesis.