Autopsy-Confirmed Familial Early-Onset Alzheimer Disease Caused by the L153V Presenilin 1 Mutation | Dementia and Cognitive Impairment | JAMA Neurology | JAMA Network
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Original Contribution
June 2001

Autopsy-Confirmed Familial Early-Onset Alzheimer Disease Caused by the L153V Presenilin 1 Mutation

Author Affiliations

From the Dementia Research Group, Institute of Neurology (Drs Janssen, Fox, Harvey, and Rossor), the Departments of Neuropathology (Dr Lantos) and Neuroscience (Dr Hanger), Institute of Psychiatry, the Medical Research Council Prion Unit, Department of Neurogenetics, Imperial College School of Medicine (Messrs Beck and Dickinson, Ms Campbell, and Dr Collinge), and the Departments of Clinical Neuropsychology (Dr Cipolotti) and Neuroradiology (Dr Stevens), National Hospital for Neurology and Neurosurgery, London, England.

Arch Neurol. 2001;58(6):953-958. doi:10.1001/archneur.58.6.953

Background  Three affected individuals 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 [CI], 34.6-36.0 years); at death, 44.0 years (95% CI, 39.1-48.9 years). Mean duration of illness was 8.3 years (95% CI, 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.