title: MM2-thalamic Creutzfeldt-Jakob disease: neuropathological, biochemical and transmission studies identify a distinctive prion strain.
abstract: In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrP(Sc) ) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrP(Sc)  and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrP(Sc)  are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia. We observed two young patients with MM2-thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrP(Sc) . Challenge of transgenic mice expressing 129MM human PrP showed that MM2-thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2-cortical sCJD. The affected mice showed deposition of type 2A PrP(Sc) , a scenario that is unprecedented in this mouse line. These data indicate that MM2-thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2-cortical form.
authors.affiliation: Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Moda
authors.forename: Silvia
authors.initials: S
authors.lastname: Suardi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Fede
authors.forename: Antonio
authors.initials: A
authors.lastname: Indaco
authors.forename: Lucia
authors.initials: L
authors.lastname: Limido
authors.forename: Chiara
authors.initials: C
authors.lastname: Vimercati
authors.forename: Margherita
authors.initials: M
authors.lastname: Ruggerone
authors.forename: Ilaria
authors.initials: I
authors.lastname: Campagnani
authors.forename: Jan
authors.initials: J
authors.lastname: Langeveld
authors.forename: Alessandro
authors.initials: A
authors.lastname: Terruzzi
authors.forename: Antonio
authors.initials: A
authors.lastname: Brambilla
authors.forename: Pietro
authors.initials: P
authors.lastname: Zerbi
authors.forename: Paolo
authors.initials: P
authors.lastname: Fociani
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Bishop
authors.forename: Robert G
authors.initials: RG
authors.lastname: Will
authors.forename: Jean C
authors.initials: JC
authors.lastname: Manson
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giaccone
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
mesh_terms: D000328:Adult; D000818:Animals; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000473:pathology / Q000635:transmission; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011110:Polymorphism, Genetic / Q000235:genetics*; D011328:Prions / Q000235:genetics* / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: D005904:Glial Fibrillary Acidic Protein; D011328:Prions