title: Autopsy-confirmed familial early-onset Alzheimer disease caused by the l153V presenilin 1 mutation.
abstract: 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.
authors.affiliation: Dementia Research Group, Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, England.
authors.forename: J C
authors.initials: JC
authors.lastname: Janssen
authors.forename: P L
authors.initials: PL
authors.lastname: Lantos
authors.forename: N C
authors.initials: NC
authors.lastname: Fox
authors.forename: R J
authors.initials: RJ
authors.lastname: Harvey
authors.forename: J
authors.initials: J
authors.lastname: Beck
authors.forename: A
authors.initials: A
authors.lastname: Dickinson
authors.forename: T A
authors.initials: TA
authors.lastname: Campbell
authors.forename: J
authors.initials: J
authors.lastname: Collinge
authors.forename: D P
authors.initials: DP
authors.lastname: Hanger
authors.forename: L
authors.initials: L
authors.lastname: Cipolotti
authors.forename: J M
authors.initials: JM
authors.lastname: Stevens
authors.forename: M N
authors.initials: MN
authors.lastname: Rossor
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D058225:Plaque, Amyloid / Q000473:pathology; D053764:Presenilin-1
chemical_list: D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1