Alzheimer's disease with spastic paraparesis and 'cotton wool' plaques: two pedigrees with PS-1 exon 9 deletions.
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.
Brooks
William S
WS
Centre for Education and Research on Ageing, University of Sydney and Concord Hospital, New South Wales, Australia. w.brooks@unsw.edu.au
Kwok
John B J
JB
Kril
Jillian J
JJ
Broe
G Anthony
GA
Blumbergs
Peter C
PC
Tannenberg
Anthony E
AE
Lamont
Phillipa J
PJ
Hedges
Philippa
P
Schofield
Peter R
PR
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
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1