title: A novel mutation in the predicted TMIII domain of the PSEN2 gene in an Italian pedigree with atypical Alzheimer's disease.
abstract: Alzheimer's disease (AD) is characterized by accumulation of toxic amyloid-beta (Abeta) in the brain, with neuronal death, and an associated increased Abeta(42/40) ratio. Several mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid-beta precursor protein are involved in the etiology of familial AD (FAD); these mutations alter the Abeta(42/40) ratio and promote apoptosis. We describe an Italian pedigree linked to a novel mutation (S175C) at the third transmembrane domain of PSEN2. Clinical phenotype in these individuals is characterized by fast cognitive decline with progressive memory impairment, early involvement of executive functions, behavioral disturbances, and extrapyramidal signs.
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Piscopo
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Talarico
authors.forename: Alessio
authors.initials: A
authors.lastname: Crestini
authors.forename: Marina
authors.initials: M
authors.lastname: Gasparini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Malvezzi-Campeggi
authors.forename: Elisa
authors.initials: E
authors.lastname: Piacentini
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Lenzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bruno
authors.forename: Annamaria
authors.initials: A
authors.lastname: Confaloni
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics*; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D010375:Pedigree; D053766:Presenilin-2 / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics*; D012694:Serine / Q000235:genetics
chemical_list: C508861:PSEN2 protein, human; D053766:Presenilin-2; D012694:Serine; D003545:Cysteine