title: Early-onset Alzheimer's disease with a de novo mutation in the presenilin 1 gene.
abstract: A 32-year-old woman diagnosed with very rapidly progressing early-onset Alzheimer's disease (EOAD), age of onset 29 years, and S170F mutation in presenilin 1 gene (PSEN1) is presented. Neuroimaging conducted 2 years after the first symptoms was typical for the advanced stage of Alzheimer's disease (AD), showing cortical brain atrophy, particularly within hippocampus, frontal and temporal cortex. The unaffected parents of the proband are not carriers of the mutation. The paternity was confirmed by microsatellite typing, strongly suggesting de novo origin of S170F mutation. In silico modeling of S170F mutation impact on presenilin 1 (PS1) transmembrane structure indicates that the mutation considerably alters putative interactions of PS1 with other proteins within gamma-secretase complex.
authors.affiliation: Department of Neurodegenerative Disorders, Medical Research Center, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warszawa, Poland.
authors.forename: M P
authors.initials: MP
authors.lastname: Golan
authors.forename: M
authors.initials: M
authors.lastname: Styczyńska
authors.forename: K
authors.initials: K
authors.lastname: Jóźwiak
authors.forename: J
authors.initials: J
authors.lastname: Walecki
authors.forename: A
authors.initials: A
authors.lastname: Maruszak
authors.forename: J
authors.initials: J
authors.lastname: Pniewski
authors.forename: R
authors.initials: R
authors.lastname: Lugiewicz
authors.forename: S
authors.initials: S
authors.lastname: Filipek
authors.forename: C
authors.initials: C
authors.lastname: Zekanowski
authors.forename: M
authors.initials: M
authors.lastname: Barcikowska
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D001921:Brain / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008958:Models, Molecular; D009154:Mutation; D010649:Phenylalanine; D053764:Presenilin-1 / Q000235:genetics*; D012694:Serine; D013997:Time Factors
chemical_list: D053764:Presenilin-1; D012694:Serine; D010649:Phenylalanine