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

• Published in: Archives of neurology (Chicago) Vol. 58; no. 6; pp. 953 - 958
• Main Authors: Janssen, John C, Lantos, Peter L, Fox, Nicholas C, Harvey, Richard J, Beck, Jonathan, Dickinson, Andrew, Campbell, Tracey A, Collinge, John, Hanger, Diane P, Cipolotti, Lisa, Stevens, John M, Rossor, Martin N
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 01.06.2001
• Subjects: Adult; Aged; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Amyloid beta-Peptides - metabolism; Biological and medical sciences; Brain - pathology; Confidence Intervals; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Humans; Lewy Bodies - pathology; Male; Medical sciences; Membrane Proteins - genetics; Middle Aged; Mutation, Missense - genetics; Neurology; Pedigree; Plaque, Amyloid - pathology; Presenilin-1; Human; Nervous system diseases; Alzheimer disease; Family study; Presenilin; Cerebral disorder; Pathology; Age of onset; Gene; Autopsy; Etiology; Central nervous system disease; Early; Degenerative disease; Mutation
• ISSN: 0003-9942; 2168-6149; 1538-3687; 2168-6157
• 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.Arch Neurol. 2001;58:953-958-->