title: Novel insertional presenilin 1 mutation causing Alzheimer disease with spastic paraparesis.
abstract: A four-generation pedigree exhibiting early-onset autosomal dominant Alzheimer disease (AD) with spastic paraplegia, dystonia, and dysarthria due to a novel 6-nucleotide insertional mutation in exon 3 of the presenilin 1 gene (PS1) is described. Serial examinations, PET scans, and autopsy revealed that the mutation in this highly conserved portion of PS1 causes an aggressive dementia that maintains the usual regional hierarchy of disease pathology while extending abnormalities into more widespread brain areas than typically seen in AD.
authors.affiliation: Departments of Neurology, University of Michigan, Ann Arbor 48109, USA.
authors.forename: P
authors.initials: P
authors.lastname: Moretti
authors.forename: A P
authors.initials: AP
authors.lastname: Lieberman
authors.forename: E A
authors.initials: EA
authors.lastname: Wilde
authors.forename: B I
authors.initials: BI
authors.lastname: Giordani
authors.forename: K J
authors.initials: KJ
authors.lastname: Kluin
authors.forename: R A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: S
authors.initials: S
authors.lastname: Minoshima
authors.forename: D E
authors.initials: DE
authors.lastname: Kuhl
authors.forename: W K
authors.initials: WK
authors.lastname: Seltzer
authors.forename: N L
authors.initials: NL
authors.lastname: Foster
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D019943:Amino Acid Substitution; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D003062:Codon / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008824:Michigan; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009483:Neuropsychological Tests; D020336:Paraparesis, Spastic / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D053764:Presenilin-1; D014055:Tomography, Emission-Computed
chemical_list: D003062:Codon; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1