BACKGROUND: Intronic variant rs564309 in tripartite motif containing 11 (TRIM11) is associated with clinical phenotypic differences in progressive supranuclear palsy (PSP), whereby the minor allele (A) is more common in atypical PSP than typical PSP (PSP-Richardson's syndrome). However, rs564309 has not been investigated relative to neuropathological outcomes. OBJECTIVE: Evaluate the association of rs564309 with the neuropathologically assessed severity of tau pathology, as measured by semi-quantitative scores for neurofibrillary tangles, tufted astrocytes, neuropil threads, and oligodendroglial coiled bodies. METHODS: 797 neuropathologically confirmed PSP cases were genotyped for TRIM11 rs564309 and assessed for tau pathology across 20 neuroanatomical regions. Tau pathology measures and age at death were examined for association with TRIM11 rs564309-A using multivariable linear regression models. RESULTS: TRIM11 rs564309-A was associated with increased neurofibrillary tangles pathology (P = 0.050), but was not significantly associated with age at death, neuropil threads, coiled bodies, or tufted astrocytes tau pathology scores. CONCLUSIONS: TRIM11 rs564309 may influence burden of neurofibrillary tangles tau pathology in PSP; further study is warranted.
BACKGROUND: Intronic variant rs564309 in tripartite motif containing 11 (TRIM11) is associated with clinical phenotypic differences in progressive supranuclear palsy (PSP), whereby the minor allele (A) is more common in atypical PSP than typical PSP (PSP-Richardson's syndrome). However, rs564309 has not been investigated relative to neuropathological outcomes. OBJECTIVE: Evaluate the association of rs564309 with the neuropathologically assessed severity of tau pathology, as measured by semi-quantitative scores for neurofibrillary tangles, tufted astrocytes, neuropil threads, and oligodendroglial coiled bodies. METHODS: 797 neuropathologically confirmed PSP cases were genotyped for TRIM11 rs564309 and assessed for tau pathology across 20 neuroanatomical regions. Tau pathology measures and age at death were examined for association with TRIM11 rs564309-A using multivariable linear regression models. RESULTS: TRIM11 rs564309-A was associated with increased neurofibrillary tangles pathology (P = 0.050), but was not significantly associated with age at death, neuropil threads, coiled bodies, or tufted astrocytes tau pathology scores. CONCLUSIONS: TRIM11 rs564309 may influence burden of neurofibrillary tangles tau pathology in PSP; further study is warranted.
Authors: Günter U Höglinger; Gesine Respondek; Maria Stamelou; Carolin Kurz; Keith A Josephs; Anthony E Lang; Brit Mollenhauer; Ulrich Müller; Christer Nilsson; Jennifer L Whitwell; Thomas Arzberger; Elisabet Englund; Ellen Gelpi; Armin Giese; David J Irwin; Wassilios G Meissner; Alexander Pantelyat; Alex Rajput; John C van Swieten; Claire Troakes; Angelo Antonini; Kailash P Bhatia; Yvette Bordelon; Yaroslau Compta; Jean-Christophe Corvol; Carlo Colosimo; Dennis W Dickson; Richard Dodel; Leslie Ferguson; Murray Grossman; Jan Kassubek; Florian Krismer; Johannes Levin; Stefan Lorenzl; Huw R Morris; Peter Nestor; Wolfgang H Oertel; Werner Poewe; Gil Rabinovici; James B Rowe; Gerard D Schellenberg; Klaus Seppi; Thilo van Eimeren; Gregor K Wenning; Adam L Boxer; Lawrence I Golbe; Irene Litvan Journal: Mov Disord Date: 2017-05-03 Impact factor: 10.338
Authors: Melissa E Murray; Val J Lowe; Neill R Graff-Radford; Amanda M Liesinger; Ashley Cannon; Scott A Przybelski; Bhupendra Rawal; Joseph E Parisi; Ronald C Petersen; Kejal Kantarci; Owen A Ross; Ranjan Duara; David S Knopman; Clifford R Jack; Dennis W Dickson Journal: Brain Date: 2015-03-23 Impact factor: 13.501
Authors: Edwin Jabbari; John Woodside; Manuela M X Tan; Maryam Shoai; Alan Pittman; Raffaele Ferrari; Kin Y Mok; David Zhang; Regina H Reynolds; Rohan de Silva; Max-Joseph Grimm; Gesine Respondek; Ulrich Müller; Safa Al-Sarraj; Stephen M Gentleman; Andrew J Lees; Thomas T Warner; John Hardy; Tamas Revesz; Günter U Höglinger; Janice L Holton; Mina Ryten; Huw R Morris Journal: Ann Neurol Date: 2018-09-15 Impact factor: 10.422
Authors: Edwin Jabbari; John Woodside; Manuela M X Tan; Nicola Pavese; Oliver Bandmann; Boyd C P Ghosh; Luke A Massey; Erica Capps; Tom T Warner; Andrew J Lees; Tamas Revesz; Janice L Holton; Nigel M Williams; Donald G Grosset; Huw R Morris Journal: Mov Disord Date: 2019-07-12 Impact factor: 10.338
Authors: Na Zhao; Chia-Chen Liu; Alexandra J Van Ingelgom; Cynthia Linares; Aishe Kurti; Joshua A Knight; Michael G Heckman; Nancy N Diehl; Mitsuru Shinohara; Yuka A Martens; Olivia N Attrebi; Leonard Petrucelli; John D Fryer; Zbigniew K Wszolek; Neill R Graff-Radford; Richard J Caselli; Monica Y Sanchez-Contreras; Rosa Rademakers; Melissa E Murray; Shunsuke Koga; Dennis W Dickson; Owen A Ross; Guojun Bu Journal: Nat Commun Date: 2018-10-22 Impact factor: 17.694