Brain, Vol. 118, No. 1, 185-205, 1995
© 1995 Oxford University Press
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Chromosome 14 linked familial Alzheimer's disease
A clinico-pathological study of a single pedigree
1The Dementia Research Group, Department of Neurology, St Mary's Hospital Medical School, Imperial College London 2MRC Cyclotron Unit, Hammersmith Hospital London 3National Hospital for Neurology and Neurosurgery London 4Department of Neurology, Manchester Royal Infirmary Manchester 5Department of Neuropathology, Runwell Hospital Wickford, UK
Correspondence to:
Dr Martin Rossor, The National Hospital for Neurology and Neurosurgery, Queen Square, London SWI SBN, UK
The Clinical features of three affected members of a British pedigree with familial Alzheimer's disease are presented. This pedigree is one of six included in an earlier study which demonstrated linkage to chromosome 14. The individuals were investigated clinically and neuropsychologically, using both PET and MRI over a 4-year period. Further information from three deceased individuals was obtained, including histopathological confirmation of Alzheimer's disease in one case which came to autopsy. The mean age at onset for this family was 43 years. Neurological examination revealed myoclonic jerks in all cases, and one patient was documented to have seizures. Strikingly similar neuropsychological profiles were observed, characterized by an initial memory deficit with early dyscalculia and an impairment in speech production with relative absence of anomia. All individuals showed mild degrees of cerebral atrophy and two individuals had periventricular white matter lesions. PET scanning using [18F]fluorodeoxyglucose showed parieto-temporal hypometabolism in all cases and the two severely affected patients with speech production changes had additional left-sided frontal hypometabolism involving Broca's area. The least affected case initially had a more asymmetrical reduction in metabolism in the left inferior temporal and supramarginal gyri; a follow-up scan showed that this deficit had become bilateral and more severe. These clinical and neuroimaging features have not been previously reported in chromosome 14 linked pedigrees; the phenotypic variability between families suggests allelic heterogeneity at the chromosome 14 locus.
familial Alzheimer's disease; PET; cerebral metabolic rate for glucose (CMRglu); chromosome 14; speech production deficit
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