title: A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease, seizures and cotton wool plaques, but not spastic paraparesis.
abstract: Over 100 mutations in the presenilin-1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Abeta was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.
authors.affiliation: Department of Pathology, SUNY Upstate Medical University, 750 E Adams St, Syracuse, NY 13210, USA. shrimpta@upstate.edu
authors.forename: Antony E
authors.initials: AE
authors.lastname: Shrimpton
authors.forename: Robert L
authors.initials: RL
authors.lastname: Schelper
authors.forename: Reinhold P
authors.initials: RP
authors.lastname: Linke
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Richard
authors.initials: R
authors.lastname: Crook
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishizawa
authors.forename: Richard L
authors.initials: RL
authors.lastname: Davis
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000473:pathology; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D020125:Mutation, Missense; D020336:Paraparesis, Spastic / Q000473:pathology*; D010375:Pedigree; D058225:Plaque, Amyloid / Q000473:pathology*; D017354:Point Mutation; D053764:Presenilin-1 / Q000737:chemistry / Q000235:genetics*; D012640:Seizures / Q000209:etiology*
chemical_list: D016229:Amyloid beta-Peptides; D053764:Presenilin-1