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Autopsy-confirmed familial early-onset Alzheimer disease caused by the L153V presenilin 1 mutation

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journal contribution
posted on 2001-06-01, 00:00 authored by J C Janssen, P L Lantos, N C Fox, Richard HarveyRichard Harvey, J Beck, A Dickinson, T A Campbell, J Collinge, D P Hanger, L Cipolotti, J M Stevens, M N Rossor
Background: Three affected individuais are described from a small English kindred with early-onset autosomal dominant familial Alzheimer disease (FAD) caused by a leucine-to-valine change at codon 153 (L153V) of the presenilin 1 (PSEN1) gene. Methods: Clinical information on the pedigree was collected directly from family members and from hospital records. Samples of DNA were screened by means of direct sequencing of all coding exons of PSEN1. One patient underwent neuropathological examination. Results: Mean age at onset of symptoms was 35.3 years (95% confidence interval [C1], 34.6-36.0 years); at death, 44.0 years (95% C1, 39.1-48.9 years). Mean duration of illness was 8.3 years (95% C1, 4.7-11.9 years). Myoclonus was a late feature in 1 patient; seizures were not reported in any subjects. Spastic paraparesis and extrapyramidal signs were absent. The neuropsychometric profile of 1 patient showed relatively preserved naming skills in the setting of global cognitive deficits. Results of neuropathological examination demonstrated the signature lesions of Alzheimer disease and the presence of occasional cortical Lewy bodies. Conclusions: The PSEN1 L153V mutation lies in the main mutation cluster of PSEN1 in the second transmembrane domain. It causes early-onset FAD with clinical features similar to those of other reported FAD pedigrees.



Archives of neurology






953 - 958


American Medical Association


Chicago, Ill.





Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2001, American Medical Association