title: Early-onset dementia with Lewy bodies.
abstract: The clinical and neuropathological characteristics of an atypical form of dementia with Lewy bodies (DLB) are described. The proband experienced difficulties in her school performance at 13 years of age. Neurological examination revealed cognitive dysfunction, dysarthria, parkinsonism and myoclonus. By age 14 years, the symptoms had worsened markedly and the proband died at age 15 years. On neuropathological examination, the brain was severely atrophic. Numerous intracytoplasmic and intraneuritic Lewy bodies, as well as Lewy neurites, were present throughout the cerebral cortex and subcortical nuclel; vacuolar changes were seen in the upper layers of the neocortex and severe neuronal loss and gliosis were evident in the cerebral cortex and substantia nigra. Lewy bodies and Lewy neurites were strongly immunoreactive for alpha-synuclein and ubiquitin. Lewy bodies were composed of filamentous and granular material and isolated filaments were decorated by alpha-synuclein antibodies. Immunohistochemistry for tau or beta-amyloid yielded negative results. The etiology of this atypical form of DLB is unknown, since there was no family history and since sequencing of the exonic regions of alpha-Synuclein, beta-Synuclein, Synphilin-1, Parkin, Ubiquitin C-terminal hydrolase L1 and Neurofilament-M failed to reveal a pathogenic mutation. This study provides further evidence of the clinical and pathological heterogeneity of DLB.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 635 Barnhill Drive, B029D, Indianapolis, IN 46202, USA.
authors.forename: Masaki
authors.initials: M
authors.lastname: Takao
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Yoshida
authors.forename: Pedro
authors.initials: P
authors.lastname: Piccardo
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Narain
authors.forename: Jill R
authors.initials: JR
authors.lastname: Murrell
authors.forename: Ruben
authors.initials: R
authors.lastname: Vidal
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Glazier
authors.forename: Ross
authors.initials: R
authors.lastname: Jakes
authors.forename: Miho
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Spillantini
authors.forename: R Anthony
authors.initials: RA
authors.lastname: Crowther
authors.forename: Michel
authors.initials: M
authors.lastname: Goedert
authors.forename: Atsuo
authors.initials: A
authors.lastname: Koto
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001921:Brain / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000473:pathology; D020961:Lewy Body Disease / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; C497607:SNCB protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein