Salvatore Spina1, Daniel R Schonhaut2, Bradley F Boeve2, William W Seeley2, Rik Ossenkoppele2, James P O'Neil2, Andreas Lazaris2, Howard J Rosen2, Adam L Boxer2, David C Perry2, Bruce L Miller2, Dennis W Dickson2, Joseph E Parisi2, William J Jagust2, Melissa E Murray2, Gil D Rabinovici2. 1. From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL. Salvatore.Spina@ucsf.edu. 2. From the Memory and Aging Center (S.S., D.R.S., W.W.S., R.O., A.L., H.J.R., A.L.B., D.C.P., B.L.M., G.D.R.), Department of Neurology, and Department of Pathology (W.W.S), University of California, San Francisco; Department of Neurology (B.F.B., J.E.P.), Mayo Clinic, Rochester, MN; Helen Wills Neuroscience Institute (R.O., W.J.J., G.D.R.), University of California Berkeley; Alzheimercenter (R.O.), VU University Medical Center, Amsterdam, the Netherlands; Lawrence Berkeley National Laboratory (J.P.O., W.J.J., M.E.M., G.D.R.), Berkeley, CA; and Department of Pathology (D.W.D.), Mayo Clinic, Jacksonville, FL.
Abstract
OBJECTIVE: To assess the efficacy of [18F]AV1451 PET in visualizing tau pathology in vivo in a patient with frontotemporal dementia (FTD) associated with the V337M microtubule-associated protein tau (MAPT) mutation. METHODS: MAPT mutations are associated with the deposition of hyperphosphorylated tau protein in neurons and glia. The PET tracer [18F]AV1451 binds with high affinity to paired helical filaments tau that comprises neurofibrillary tangles in Alzheimer disease (AD), while postmortem studies suggest lower or absent binding to the tau filaments of the majority of non-AD tauopathies. We describe clinical, structural MRI, and [18F]AV1451 PET findings in a V337M MAPT mutation carrier affected by FTD and pathologic findings in his affected mother and in an unrelated V337M MAPT carrier also affected with FTD. The biochemical similarity between paired helical filament tau in AD and MAPT V337M predicts that the tau pathology associated with this mutation constitutes a compelling target for [18F]AV1451 imaging. RESULTS: We found a strong association between topography and degree of [18F]AV1451 tracer retention in the proband and distribution of tau pathology in the brain of the proband's mother and the unrelated V337M mutation carrier. We also found a significant correlation between the degree of regional MRI brain atrophy and the extent of [18F]AV1451 binding in the proband and a strong association between the proband's clinical presentation and the extent of regional brain atrophy and tau accumulation as assessed by structural brain MRI and [18F]AV1451PET. CONCLUSION: Our study supports the usefulness of [18F]AV1451 to characterize tau pathology in at least a subset of pathogenic MAPT mutations.
OBJECTIVE: To assess the efficacy of [18F]AV1451 PET in visualizing tau pathology in vivo in a patient with frontotemporal dementia (FTD) associated with the V337M microtubule-associated protein tau (MAPT) mutation. METHODS: MAPT mutations are associated with the deposition of hyperphosphorylated tau protein in neurons and glia. The PET tracer [18F]AV1451 binds with high affinity to paired helical filaments tau that comprises neurofibrillary tangles in Alzheimer disease (AD), while postmortem studies suggest lower or absent binding to the tau filaments of the majority of non-AD tauopathies. We describe clinical, structural MRI, and [18F]AV1451 PET findings in a V337M MAPT mutation carrier affected by FTD and pathologic findings in his affected mother and in an unrelated V337M MAPT carrier also affected with FTD. The biochemical similarity between paired helical filament tau in AD and MAPT V337M predicts that the tau pathology associated with this mutation constitutes a compelling target for [18F]AV1451 imaging. RESULTS: We found a strong association between topography and degree of [18F]AV1451 tracer retention in the proband and distribution of tau pathology in the brain of the proband's mother and the unrelated V337M mutation carrier. We also found a significant correlation between the degree of regional MRI brain atrophy and the extent of [18F]AV1451 binding in the proband and a strong association between the proband's clinical presentation and the extent of regional brain atrophy and tau accumulation as assessed by structural brain MRI and [18F]AV1451PET. CONCLUSION: Our study supports the usefulness of [18F]AV1451 to characterize tau pathology in at least a subset of pathogenic MAPT mutations.
Authors: M L Gorno-Tempini; A E Hillis; S Weintraub; A Kertesz; M Mendez; S F Cappa; J M Ogar; J D Rohrer; S Black; B F Boeve; F Manes; N F Dronkers; R Vandenberghe; K Rascovsky; K Patterson; B L Miller; D S Knopman; J R Hodges; M M Mesulam; M Grossman Journal: Neurology Date: 2011-02-16 Impact factor: 9.910
Authors: David T Chien; Shadfar Bahri; A Katrin Szardenings; Joseph C Walsh; Fanrong Mu; Min-Ying Su; William R Shankle; Arkadij Elizarov; Hartmuth C Kolb Journal: J Alzheimers Dis Date: 2013 Impact factor: 4.472
Authors: Chun-Fang Xia; Janna Arteaga; Gang Chen; Umesh Gangadharmath; Luis F Gomez; Dhanalakshmi Kasi; Chung Lam; Qianwa Liang; Changhui Liu; Vani P Mocharla; Fanrong Mu; Anjana Sinha; Helen Su; A Katrin Szardenings; Joseph C Walsh; Eric Wang; Chul Yu; Wei Zhang; Tieming Zhao; Hartmuth C Kolb Journal: Alzheimers Dement Date: 2013-02-12 Impact factor: 21.566
Authors: Keith A Josephs; Jennifer L Whitwell; Pawel Tacik; Joseph R Duffy; Matthew L Senjem; Nirubol Tosakulwong; Clifford R Jack; Val Lowe; Dennis W Dickson; Melissa E Murray Journal: Acta Neuropathol Date: 2016-09-19 Impact factor: 17.088
Authors: Leslie M Shaw; Hugo Vanderstichele; Malgorzata Knapik-Czajka; Christopher M Clark; Paul S Aisen; Ronald C Petersen; Kaj Blennow; Holly Soares; Adam Simon; Piotr Lewczuk; Robert Dean; Eric Siemers; William Potter; Virginia M-Y Lee; John Q Trojanowski Journal: Ann Neurol Date: 2009-04 Impact factor: 10.422
Authors: Keith A Johnson; Aaron Schultz; Rebecca A Betensky; J Alex Becker; Jorge Sepulcre; Dorene Rentz; Elizabeth Mormino; Jasmeer Chhatwal; Rebecca Amariglio; Kate Papp; Gad Marshall; Mark Albers; Samantha Mauro; Lesley Pepin; Jonathan Alverio; Kelly Judge; Marlie Philiossaint; Timothy Shoup; Daniel Yokell; Bradford Dickerson; Teresa Gomez-Isla; Bradley Hyman; Neil Vasdev; Reisa Sperling Journal: Ann Neurol Date: 2015-12-15 Impact factor: 10.422
Authors: M G Spillantini; J R Murrell; M Goedert; M R Farlow; A Klug; B Ghetti Journal: Proc Natl Acad Sci U S A Date: 1998-06-23 Impact factor: 11.205
Authors: Ruben Smith; Andreas Puschmann; Michael Schöll; Tomas Ohlsson; John van Swieten; Michael Honer; Elisabet Englund; Oskar Hansson Journal: Brain Date: 2016-06-29 Impact factor: 13.501
Authors: Jennifer S Yokoyama; Virginia E Sturm; Luke W Bonham; Eric Klein; Konstantinos Arfanakis; Lei Yu; Giovanni Coppola; Joel H Kramer; David A Bennett; Bruce L Miller; Dena B Dubal Journal: Ann Clin Transl Neurol Date: 2015-01-26 Impact factor: 5.430
Authors: Val J Lowe; Geoffry Curran; Ping Fang; Amanda M Liesinger; Keith A Josephs; Joseph E Parisi; Kejal Kantarci; Bradley F Boeve; Mukesh K Pandey; Tyler Bruinsma; David S Knopman; David T Jones; Leonard Petrucelli; Casey N Cook; Neill R Graff-Radford; Dennis W Dickson; Ronald C Petersen; Clifford R Jack; Melissa E Murray Journal: Acta Neuropathol Commun Date: 2016-06-13 Impact factor: 7.801
Authors: Adam M Staffaroni; Fanny M Elahi; Dana McDermott; Kacey Marton; Elissaios Karageorgiou; Simone Sacco; Matteo Paoletti; Eduardo Caverzasi; Christopher P Hess; Howard J Rosen; Michael D Geschwind Journal: Semin Neurol Date: 2017-12-05 Impact factor: 3.420
Authors: David N Soleimani-Meigooni; Leonardo Iaccarino; Renaud La Joie; Suzanne Baker; Viktoriya Bourakova; Adam L Boxer; Lauren Edwards; Rana Eser; Maria-Luisa Gorno-Tempini; William J Jagust; Mustafa Janabi; Joel H Kramer; Orit H Lesman-Segev; Taylor Mellinger; Bruce L Miller; Julie Pham; Howard J Rosen; Salvatore Spina; William W Seeley; Amelia Strom; Lea T Grinberg; Gil D Rabinovici Journal: Brain Date: 2020-12-05 Impact factor: 13.501
Authors: Hye Joo Son; Jungsu S Oh; Jee Hoon Roh; Sang Won Seo; Minyoung Oh; Sang Ju Lee; Seung Jun Oh; Jae Seung Kim Journal: Eur J Nucl Med Mol Imaging Date: 2018-08-14 Impact factor: 9.236
Authors: Gregory S Day; Brian A Gordon; Richard J Perrin; Nigel J Cairns; Helen Beaumont; Katherine Schwetye; Cole Ferguson; Namita Sinha; Robert Bucelli; Erik S Musiek; Nupur Ghoshal; Maria R Ponisio; Benjamin Vincent; Shruti Mishra; Kelley Jackson; John C Morris; Tammie L S Benzinger; Beau M Ances Journal: Neurology Date: 2018-02-07 Impact factor: 9.910