title: A novel PSEN1 mutation (I238M) associated with early-onset Alzheimer's disease in an African-American woman.
abstract: Mutations in PSEN1 are the most common cause of autosomal dominant familial Alzheimer's disease (FAD). We describe an African-American woman with a family history consistent with FAD who began to experience cognitive decline at age 50. Her clinical presentation, MRI, FDG-PET, and PIB-PET scan findings were consistent with AD and she was found to have a novel I238M substitution in PSEN1. As this mutation caused increased production of Aβ42 in an in vitro assay, was not present in two population databases, and is conserved across species, it is likely to be pathogenic for FAD.
authors.affiliation: Department of Neurology, Singapore General Hospital, Singapore.
authors.forename: Simon Kang Seng
authors.initials: SK
authors.lastname: Ting
authors.affiliation: Departments of Radiology and Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Tammie
authors.initials: T
authors.lastname: Benzinger
authors.affiliation: Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kepe
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Fagan
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Easton Center for Alzheimer's Disease Research at UCLA, Los Angeles, CA, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Verna
authors.initials: V
authors.lastname: Porter
authors.affiliation: Department of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
authors.forename: Silva
authors.initials: S
authors.lastname: Hecimovic
authors.affiliation: Department of Psychiatry, Washington University, St. Louis, MO, USA.
authors.forename: Suma
authors.initials: S
authors.lastname: Chakraverty
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Easton Center for Alzheimer's Disease Research at UCLA, Los Angeles, CA, USA.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Alvarez-Retuerto
authors.affiliation: Department of Psychiatry, Washington University, St. Louis, MO, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Easton Center for Alzheimer's Disease Research at UCLA, Los Angeles, CA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Ringman
mesh_terms: D001741:Black or African American; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D000814:Aniline Compounds; D052160:Benzothiazoles; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007532:Isoleucine / Q000235:genetics*; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D049268:Positron-Emission Tomography; D053764:Presenilin-1 / Q000235:genetics*; D013844:Thiazoles; D014162:Transfection
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D052160:Benzothiazoles; C508853:PSEN1 protein, human; D053764:Presenilin-1; D013844:Thiazoles; D007532:Isoleucine; D049452:Green Fluorescent Proteins; D008715:Methionine
keywords: African; Alzheimer's disease; PIB-PET; PSEN1; amyloid-β$_{42}$; autosomal dominant; familial; gamma-secretase; in vitro; presenilin-1