title: Alzheimer's disease with spastic paraparesis and 'cotton wool' plaques: two pedigrees with PS-1 exon 9 deletions.
abstract: Several pedigrees have recently been reported in which dominantly inherited familial Alzheimer's disease is associated in some family members with spastic paraparesis and non-neuritic 'cotton wool' plaques. Here we report clinical, genetic and neuropathological findings in two further large pedigrees in which this combination of phenotypes is associated with a deletion of exon 9 of the presenilin-1 (PS-1) gene caused by mutations at the splice acceptor site. In both pedigrees, individuals with paraparesis at presentation had a later than average age at onset of symptoms. In addition, one subject with paraparesis had a much less prominent dementia syndrome than his dementia-affected siblings. As PS-1 mutations are almost always associated with a particularly aggressive form of presenile dementia, these findings suggest the existence of a protective or delaying factor in individuals with spastic paraparesis.
authors.affiliation: Centre for Education and Research on Ageing, University of Sydney and Concord Hospital, New South Wales, Australia. w.brooks@unsw.edu.au
authors.forename: William S
authors.initials: WS
authors.lastname: Brooks
authors.forename: John B J
authors.initials: JB
authors.lastname: Kwok
authors.forename: Jillian J
authors.initials: JJ
authors.lastname: Kril
authors.forename: G Anthony
authors.initials: GA
authors.lastname: Broe
authors.forename: Peter C
authors.initials: PC
authors.lastname: Blumbergs
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Tannenberg
authors.forename: Phillipa J
authors.initials: PJ
authors.lastname: Lamont
authors.forename: Philippa
authors.initials: P
authors.lastname: Hedges
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
mesh_terms: D000328:Adult; D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D005091:Exons; D017353:Gene Deletion; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020336:Paraparesis, Spastic / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D053764:Presenilin-1
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1