Browsing by Author "Piccardo, Pedro"

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    Early-onset Dementia with Lewy Bodies
    (Wiley, 2004-04) Takao, Masaki; Ghetti, Bernardino; Yoshida, Hirotaka; Piccardo, Pedro; Narain, Yolanda; Murrell, Jill R.; Vidal, Ruben; Glazier, Bradley S.; Jakes, Ross; Tsutsui, Miho; Grazia Spillantini, Maria; Crowther, R. Anthony; Goedert, Michel; Koto, Atsuo; Pathology and Laboratory Medicine, School of Medicine
    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.
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    PET of Brain Prion Protein Amyloid in Gerstmann–Sträussler–Scheinker Disease
    (Wiley, 2010-03) Kepe, Vladimir; Ghetti, Bernardino; Farlow, Martin R.; Bresjanac, Mara; Miller, Karen; Huang, Sung-Cheng; Wong, Koon-Pong; Murrell, Jill R.; Piccardo, Pedro; Epperson, Francine; Repovš, Grega; Smid, Lojze M.; Petrič, Andrej; Siddarth, Prabha; Liu, Jie; Satyamurthy, Nagichettiar; Small, Gary W.; Barrio, Jorge R.; Pathology and Laboratory Medicine, School of Medicine
    In vivo amyloid PET imaging was carried out on six symptomatic and asymptomatic carriers of PRNP mutations associated with the Gerstmann-Sträussler-Scheinker (GSS) disease, a rare familial neurodegenerative brain disorder demonstrating prion amyloid neuropathology, using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP). 2-Deoxy-2-[F-18]fluoro-d-glucose PET ([F-18]FDG) and magnetic resonance imaging (MRI) scans were also performed in each subject. Increased [F-18]FDDNP binding was detectable in cerebellum, neocortex and subcortical areas of all symptomatic gene carriers in close association with the experienced clinical symptoms. Parallel glucose metabolism ([F-18]FDG) reduction was observed in neocortex, basal ganglia and/or thalamus, which supports the close relationship between [F-18]FDDNP binding and neuronal dysfunction. Two asymptomatic gene carriers displayed no cortical [F-18]FDDNP binding, yet progressive [F-18]FDDNP retention in caudate nucleus and thalamus was seen at 1- and 2-year follow-up in the older asymptomatic subject. In vitro FDDNP labeling experiments on brain tissue specimens from deceased GSS subjects not participating in the in vivo studies indicated that in vivo accumulation of [F-18]FDDNP in subcortical structures, neocortices and cerebellum closely related to the distribution of prion protein pathology. These results demonstrate the feasibility of detecting prion protein accumulation in living patients with [F-18]FDDNP PET, and suggest an opportunity for its application to follow disease progression and monitor therapeutic interventions.