Variable phenotype of Alzheimer's disease with spastic paraparesis
Margaret J. Smith BSc (Hons)
Department of Pathology, The University of Melbourne, Melbourne, Australia
Mental Health Research Institute, Parkville, Australia
Mutation Research Centre, St. Vincent's Hospital, Fitzroy, Victoria, Australia
The first two authors contributed equally to this work.
Search for more papers by this authorJohn B.J. Kwok PhD
Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
The first two authors contributed equally to this work.
Search for more papers by this authorCatriona A. McLean MD
Department of Pathology, The University of Melbourne, Melbourne, Australia
Mental Health Research Institute, Parkville, Australia
Search for more papers by this authorJillian J. Kril PhD
Centre for Education and Research on Ageing, University of Sydney, and Concord Hospital, Concord, New South Wales, Australia
Search for more papers by this authorG. Anthony Broe MB, BS
Prince of Wales Hospital, Randwick, Australia
Search for more papers by this authorGarth A. Nicholson MB, BS, PhD
Molecular Medicine Laboratory, Concord Hospital, Concord, New South Wales, Australia
Search for more papers by this authorRoberto Cappai PhD
Department of Pathology, The University of Melbourne, Melbourne, Australia
Mental Health Research Institute, Parkville, Australia
Search for more papers by this authorMarianne Hallupp BSc
Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
Search for more papers by this authorRichard G.H. Cotton PhD
Mutation Research Centre, St. Vincent's Hospital, Fitzroy, Victoria, Australia
Search for more papers by this authorColin L. Masters MD
Department of Pathology, The University of Melbourne, Melbourne, Australia
Mental Health Research Institute, Parkville, Australia
Search for more papers by this authorCorresponding Author
Peter R. Schofield PhD, DSc
Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010 AustraliaSearch for more papers by this authorWilliam S. Brooks MB, BS, MPH
Centre for Education and Research on Ageing, University of Sydney, and Concord Hospital, Concord, New South Wales, Australia
Search for more papers by this authorMargaret J. Smith BSc (Hons)
Department of Pathology, The University of Melbourne, Melbourne, Australia
Mental Health Research Institute, Parkville, Australia
Mutation Research Centre, St. Vincent's Hospital, Fitzroy, Victoria, Australia
The first two authors contributed equally to this work.
Search for more papers by this authorJohn B.J. Kwok PhD
Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
The first two authors contributed equally to this work.
Search for more papers by this authorCatriona A. McLean MD
Department of Pathology, The University of Melbourne, Melbourne, Australia
Mental Health Research Institute, Parkville, Australia
Search for more papers by this authorJillian J. Kril PhD
Centre for Education and Research on Ageing, University of Sydney, and Concord Hospital, Concord, New South Wales, Australia
Search for more papers by this authorG. Anthony Broe MB, BS
Prince of Wales Hospital, Randwick, Australia
Search for more papers by this authorGarth A. Nicholson MB, BS, PhD
Molecular Medicine Laboratory, Concord Hospital, Concord, New South Wales, Australia
Search for more papers by this authorRoberto Cappai PhD
Department of Pathology, The University of Melbourne, Melbourne, Australia
Mental Health Research Institute, Parkville, Australia
Search for more papers by this authorMarianne Hallupp BSc
Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
Search for more papers by this authorRichard G.H. Cotton PhD
Mutation Research Centre, St. Vincent's Hospital, Fitzroy, Victoria, Australia
Search for more papers by this authorColin L. Masters MD
Department of Pathology, The University of Melbourne, Melbourne, Australia
Mental Health Research Institute, Parkville, Australia
Search for more papers by this authorCorresponding Author
Peter R. Schofield PhD, DSc
Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010 AustraliaSearch for more papers by this authorWilliam S. Brooks MB, BS, MPH
Centre for Education and Research on Ageing, University of Sydney, and Concord Hospital, Concord, New South Wales, Australia
Search for more papers by this authorAbstract
A variant form of Alzheimer's disease (AD), in which spastic paraparesis (SP) precedes dementia, is characterised by large, noncored, weakly neuritic Aβ-amyloid plaques resembling cotton wool balls and is caused by genomic deletion of presenilin 1 exon 9. A pedigree with a 5.9 kb exon 9 deletion shows a phenotypic spectrum including subjects with typical AD or with SP and numerous cotton wool plaques. In SP subjects, dementia onset is delayed and modified. This phenotypic variation suggests that modifying factors are associated with exon 9 deletions. Ann Neurol 2001;49:125–129
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