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.

Document Type: Original article

Affiliations: 1: Centre for Education and Research on Ageing, University of Sydney and Concord Hospital, 2: Prince of Wales Medical Research Institute, University of New South Wales, 3: Garvan Institute of Medical Research, Sydney, 4: Institute of Medical and Veterinary Science and Department of Pathology, University of Adelaide, Adelaide, 5: Queensland Medical Laboratories, Brisbane, 6: Department of Neurology, Royal Perth Hospital, Perth, 7: Lourdes Hospital, Cobbora Road, Dubbo, and 8: School of Medicine, St Vincent’s Hospital, University of New South Wales, Sydney, Australia