title: Clinical and biomarker investigation of a patient with a novel presenilin-1 mutation (A431V) in the mild cognitive impairment stage of Alzheimer's disease.
abstract: We report an individual who developed Alzheimer's disease (AD) due to a novel presenilin-1 mutation (Alanine-->Valine at codon 431). When he first presented, the patient met criteria for mild cognitive impairment but progressed over 16 months to fulfill diagnostic criteria of AD. At his first presentation, he showed widespread metabolic deficits in the posterior cingulate, lateral parietal, posterior parietal, and medial temporal regions on positron emission tomography as well as elevated tau and phospho-tau levels in cerebrospinal fluid (CSF). We suggest that functional neuroimaging and CSF biomarkers can serve as useful predictors of development of AD. Accumulation of pathologic tau isoforms and neuron death occur even in the mildest clinical stages of AD.
authors.affiliation: Division of Clinical Research, National Institute on Alcoholism, Kurihama National Hospital, Yokosuka, Kanagawa, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Matsushita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ohmori
authors.forename: Keiichi
authors.initials: K
authors.lastname: Takasugi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Matsui
authors.forename: Masahiro
authors.initials: M
authors.lastname: Maruyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwatsubo
authors.forename: Susumu
authors.initials: S
authors.lastname: Higuchi
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis*; D019788:Fluorodeoxyglucose F18; D005819:Genetic Markers; D005947:Glucose / Q000378:metabolism; D006179:Gyrus Cinguli / Q000098:blood supply / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009483:Neuropsychological Tests; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D053764:Presenilin-1; D019275:Radiopharmaceuticals; D012720:Severity of Illness Index; D014055:Tomography, Emission-Computed
chemical_list: D005819:Genetic Markers; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose