title: Progressive supranuclear palsy and tau hyperphosphorylation in a patient with a C212Y parkin mutation.
abstract: Autosomal recessive-juvenile parkinsonism (AR-JP) is one of the most common forms of familial Parkinson's disease (PD) and is related to mutations in the Park-2 gene, encoding for a protein ligase of ubiquitin, parkin. Different mutations located along the parkin gene have been observed in different AR-JP affected families, possibly interfering with the normal function of parkin and the proteasome system. Two cases of patients with AR-JP have been recently described presenting different homo- and heterozygous parkin mutations and limited tau pathology. We report here the case of a patient with clinical and pathological findings compatible with progressive supranuclear palsy (PSP), carrier of a single, heterozygous mutation of the parkin gene, and homozygous for the H1/H1 haplotype in the tau gene. Abnormal tau hyperphosphorylation has been observed in our patient brain samples, suggesting that a partial deficit of parkin, a protein with ubiquitin-ligase function, may trigger tau pathology in individuals with molecular genetic risk factors.
authors.affiliation: Centro de Biología Molecular, C.S.I.C., Universidad Autónoma de Madrid, Cantoblanco 28049, Spain. msanchezg@fjd.es
authors.forename: Marina P
authors.initials: MP
authors.lastname: Sánchez
authors.forename: Isabel
authors.initials: I
authors.lastname: Gonzalo
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
authors.forename: Justo García
authors.initials: JG
authors.lastname: De Yébenes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D006801:Humans; D007150:Immunohistochemistry; D008025:Ligases / Q000235:genetics*; D008297:Male; D010766:Phosphorylation; D017354:Point Mutation / Q000235:genetics*; D013494:Supranuclear Palsy, Progressive / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D016875:tau Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D016875:tau Proteins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases