Ignacio Illán-Gala1, Alberto Lleo2, Anna Karydas2, Adam M Staffaroni2, Henrik Zetterberg2, Rajeev Sivasankaran2, Lea T Grinberg2, Salvatore Spina2, Joel H Kramer2, Eliana M Ramos2, Giovanni Coppola2, Renaud La Joie2, Gil D Rabinovici2, David C Perry2, Maria Luisa Gorno-Tempini2, William W Seeley2, Bruce L Miller2, Howard J Rosen2, Kaj Blennow2, Adam L Boxer2, Julio C Rojas2. 1. From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles. iillan@santpau.cat. 2. From the Sant Pau Memory Unit, Department of Neurology (I.I.-G., A.L.), Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Spain; Memory and Aging Center (A.K., A.M.S., L.T.G., S.S., J.H.K., R.L.J., G.D.R., D.C.P., M.L.G.-T., W.W.S., B.L.M., H.J.R., A.L.B., J.C.R.), Department of Neurology (I.I.-G.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; UK Dementia Research Institute at UCL (H.Z.), London, UK; Novartis Institute for BioMedical Research (R.S.), Cambridge, MA; and Department of Psychiatry (E.M.R., G.C.), David Geffen School of Medicine, University of California Los Angeles.
Abstract
OBJECTIVE: To test the hypothesis that plasma total tau (t-tau) and neurofilament light chain (NfL) concentrations may have a differential role in the study of frontotemporal lobar degeneration syndromes (FTLD-S) and clinically diagnosed Alzheimer disease syndromes (AD-S), we determined their diagnostic and prognostic value in FTLD-S and AD-S and their sensitivity to pathologic diagnoses. METHODS: We measured plasma t-tau and NfL with the Simoa platform in 265 participants: 167 FTLD-S, 43 AD-S, and 55 healthy controls (HC), including 82 pathology-proven cases (50 FTLD-tau, 18 FTLD-TDP, 2 FTLD-FUS, and 12 AD) and 98 participants with amyloid PET. We compared cross-sectional and longitudinal biomarker concentrations between groups, their correlation with clinical measures of disease severity, progression, and survival, and cortical thickness. RESULTS: Plasma NfL, but not plasma t-tau, discriminated FTLD-S from HC and AD-S from HC. Both plasma NfL and t-tau were poor discriminators between FLTD-S and AD-S. In pathology-confirmed cases, plasma NfL was higher in FTLD than AD and in FTLD-TDP compared to FTLD-tau, after accounting for age and disease severity. Plasma NfL, but not plasma t-tau, predicted clinical decline and survival and correlated with regional cortical thickness in both FTLD-S and AD-S. The combination of plasma NfL with plasma t-tau did not outperform plasma NfL alone. CONCLUSION: Plasma NfL is superior to plasma t-tau for the diagnosis and prediction of clinical progression of FTLD-S and AD-S. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that plasma NfL has superior diagnostic and prognostic performance vs plasma t-tau in FTLD and AD.
OBJECTIVE: To test the hypothesis that plasma total tau (t-tau) and neurofilament light chain (NfL) concentrations may have a differential role in the study of frontotemporal lobar degeneration syndromes (FTLD-S) and clinically diagnosed Alzheimer disease syndromes (AD-S), we determined their diagnostic and prognostic value in FTLD-S and AD-S and their sensitivity to pathologic diagnoses. METHODS: We measured plasma t-tau and NfL with the Simoa platform in 265 participants: 167 FTLD-S, 43 AD-S, and 55 healthy controls (HC), including 82 pathology-proven cases (50 FTLD-tau, 18 FTLD-TDP, 2 FTLD-FUS, and 12 AD) and 98 participants with amyloid PET. We compared cross-sectional and longitudinal biomarker concentrations between groups, their correlation with clinical measures of disease severity, progression, and survival, and cortical thickness. RESULTS: Plasma NfL, but not plasma t-tau, discriminated FTLD-S from HC and AD-S from HC. Both plasma NfL and t-tau were poor discriminators between FLTD-S and AD-S. In pathology-confirmed cases, plasma NfL was higher in FTLD than AD and in FTLD-TDP compared to FTLD-tau, after accounting for age and disease severity. Plasma NfL, but not plasma t-tau, predicted clinical decline and survival and correlated with regional cortical thickness in both FTLD-S and AD-S. The combination of plasma NfL with plasma t-tau did not outperform plasma NfL alone. CONCLUSION: Plasma NfL is superior to plasma t-tau for the diagnosis and prediction of clinical progression of FTLD-S and AD-S. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that plasma NfL has superior diagnostic and prognostic performance vs plasma t-tau in FTLD and AD.
Authors: David J Irwin; Alberto Lleó; Sharon X Xie; Corey T McMillan; David A Wolk; Edward B Lee; Viviana M Van Deerlin; Leslie M Shaw; John Q Trojanowski; Murray Grossman Journal: Ann Neurol Date: 2017-08-19 Impact factor: 10.422
Authors: Renaud La Joie; Nagehan Ayakta; William W Seeley; Ewa Borys; Adam L Boxer; Charles DeCarli; Vincent Doré; Lea T Grinberg; Eric Huang; Ji-Hye Hwang; Milos D Ikonomovic; Clifford Jack; William J Jagust; Lee-Way Jin; William E Klunk; Julia Kofler; Orit H Lesman-Segev; Samuel N Lockhart; Val J Lowe; Colin L Masters; Chester A Mathis; Catriona L McLean; Bruce L Miller; Daniel Mungas; James P O'Neil; John M Olichney; Joseph E Parisi; Ronald C Petersen; Howard J Rosen; Christopher C Rowe; Salvatore Spina; Prashanthi Vemuri; Victor L Villemagne; Melissa E Murray; Gil D Rabinovici Journal: Alzheimers Dement Date: 2018-10-19 Impact factor: 21.566
Authors: Kaj Blennow; Chun Chen; Claudia Cicognola; Kristin R Wildsmith; Paul T Manser; Sandra M Sanabria Bohorquez; Zhentao Zhang; Boer Xie; Junmin Peng; Oskar Hansson; Hlin Kvartsberg; Erik Portelius; Henrik Zetterberg; Tammaryn Lashley; Gunnar Brinkmalm; Geoffrey A Kerchner; Robby M Weimer; Keqiang Ye; Kina Höglund Journal: Brain Date: 2020-02-01 Impact factor: 13.501
Authors: Emma L van der Ende; Lieke H Meeter; Jackie M Poos; Jessica L Panman; Lize C Jiskoot; Elise G P Dopper; Janne M Papma; Frank Jan de Jong; Inge M W Verberk; Charlotte Teunissen; Dimitris Rizopoulos; Carolin Heller; Rhian S Convery; Katrina M Moore; Martina Bocchetta; Mollie Neason; David M Cash; Barbara Borroni; Daniela Galimberti; Raquel Sanchez-Valle; Robert Laforce; Fermin Moreno; Matthis Synofzik; Caroline Graff; Mario Masellis; Maria Carmela Tartaglia; James B Rowe; Rik Vandenberghe; Elizabeth Finger; Fabrizio Tagliavini; Alexandre de Mendonça; Isabel Santana; Chris Butler; Simon Ducharme; Alex Gerhard; Adrian Danek; Johannes Levin; Markus Otto; Giovanni B Frisoni; Stefano Cappa; Yolande A L Pijnenburg; Jonathan D Rohrer; John C van Swieten Journal: Lancet Neurol Date: 2019-12 Impact factor: 44.182
Authors: Yolande A L Pijnenburg; Nicolaas A Verwey; Wiesje M van der Flier; Philip Scheltens; Charlotte E Teunissen Journal: Alzheimers Dement (Amst) Date: 2015-12-14
Authors: Adam M Staffaroni; Abigail O Kramer; Megan Casey; Huicong Kang; Julio C Rojas; Christina D Orrú; Byron Caughey; I Elaine Allen; Joel H Kramer; Howard J Rosen; Kaj Blennow; Henrik Zetterberg; Michael D Geschwind Journal: JAMA Neurol Date: 2019-08-01 Impact factor: 18.302
Authors: Suzanne E Schindler; James G Bollinger; Vitaliy Ovod; Kwasi G Mawuenyega; Yan Li; Brian A Gordon; David M Holtzman; John C Morris; Tammie L S Benzinger; Chengjie Xiong; Anne M Fagan; Randall J Bateman Journal: Neurology Date: 2019-08-01 Impact factor: 11.800
Authors: Peter A Ljubenkov; Adam M Staffaroni; Julio C Rojas; Isabel E Allen; Ping Wang; Hilary Heuer; Anna Karydas; John Kornak; Yann Cobigo; William W Seeley; Lea T Grinberg; Salvatore Spina; Anne M Fagan; Gina Jerome; David Knopman; Brad F Boeve; Bradford C Dickerson; Joel Kramer; Bruce Miller; Adam L Boxer; Howard J Rosen Journal: Ann Clin Transl Neurol Date: 2018-09-20 Impact factor: 4.511
Authors: Martha S Foiani; Ione Oc Woollacott; Carolin Heller; Martina Bocchetta; Amanda Heslegrave; Katrina M Dick; Lucy L Russell; Charles R Marshall; Simon Mead; Jonathan M Schott; Nick C Fox; Jason D Warren; Henrik Zetterberg; Jonathan D Rohrer Journal: J Neurol Neurosurg Psychiatry Date: 2018-02-13 Impact factor: 10.154
Authors: Adam M Staffaroni; Melanie Quintana; Barbara Wendelberger; Hilary W Heuer; Lucy L Russell; Yann Cobigo; Amy Wolf; Sheng-Yang Matt Goh; Leonard Petrucelli; Tania F Gendron; Carolin Heller; Annie L Clark; Jack Carson Taylor; Amy Wise; Elise Ong; Leah Forsberg; Danielle Brushaber; Julio C Rojas; Lawren VandeVrede; Peter Ljubenkov; Joel Kramer; Kaitlin B Casaletto; Brian Appleby; Yvette Bordelon; Hugo Botha; Bradford C Dickerson; Kimiko Domoto-Reilly; Julie A Fields; Tatiana Foroud; Ralitza Gavrilova; Daniel Geschwind; Nupur Ghoshal; Jill Goldman; Jonathon Graff-Radford; Neill Graff-Radford; Murray Grossman; Matthew G H Hall; Ging-Yuek Hsiung; Edward D Huey; David Irwin; David T Jones; Kejal Kantarci; Daniel Kaufer; David Knopman; Walter Kremers; Argentina Lario Lago; Maria I Lapid; Irene Litvan; Diane Lucente; Ian R Mackenzie; Mario F Mendez; Carly Mester; Bruce L Miller; Chiadi U Onyike; Rosa Rademakers; Vijay K Ramanan; Eliana Marisa Ramos; Meghana Rao; Katya Rascovsky; Katherine P Rankin; Erik D Roberson; Rodolfo Savica; M Carmela Tartaglia; Sandra Weintraub; Bonnie Wong; David M Cash; Arabella Bouzigues; Imogen J Swift; Georgia Peakman; Martina Bocchetta; Emily G Todd; Rhian S Convery; James B Rowe; Barbara Borroni; Daniela Galimberti; Pietro Tiraboschi; Mario Masellis; Elizabeth Finger; John C van Swieten; Harro Seelaar; Lize C Jiskoot; Sandro Sorbi; Chris R Butler; Caroline Graff; Alexander Gerhard; Tobias Langheinrich; Robert Laforce; Raquel Sanchez-Valle; Alexandre de Mendonça; Fermin Moreno; Matthis Synofzik; Rik Vandenberghe; Simon Ducharme; Isabelle Le Ber; Johannes Levin; Adrian Danek; Markus Otto; Florence Pasquier; Isabel Santana; John Kornak; Bradley F Boeve; Howard J Rosen; Jonathan D Rohrer; Adam L Boxer Journal: Nat Med Date: 2022-09-22 Impact factor: 87.241
Authors: Brandon Frank; Madeline Ally; Bailee Brekke; Henrik Zetterberg; Kaj Blennow; Michael A Sugarman; Nicholas J Ashton; Thomas K Karikari; Yorghos Tripodis; Brett Martin; Joseph N Palmisano; Eric G Steinberg; Irene Simkina; Katherine W Turk; Andrew E Budson; Maureen K O'Connor; Rhoda Au; Lee E Goldstein; Gyungah R Jun; Neil W Kowall; Thor D Stein; Ann C McKee; Ronald Killiany; Wei Qiao Qiu; Robert A Stern; Jesse Mez; Michael L Alosco Journal: Alzheimers Dement Date: 2021-12-02 Impact factor: 16.655
Authors: Eino Solje; Alberto Benussi; Emanuele Buratti; Anne M Remes; Annakaisa Haapasalo; Barbara Borroni Journal: Diagnostics (Basel) Date: 2021-04-27
Authors: Antoine Leuzy; Niklas Mattsson-Carlgren; Sebastian Palmqvist; Shorena Janelidze; Jeffrey L Dage; Oskar Hansson Journal: EMBO Mol Med Date: 2021-12-03 Impact factor: 12.137
Authors: Alberto Benussi; Nicholas J Ashton; Thomas K Karikari; Antonella Alberici; Claudia Saraceno; Roberta Ghidoni; Luisa Benussi; Henrik Zetterberg; Kaj Blennow; Barbara Borroni Journal: Alzheimers Res Ther Date: 2021-11-15 Impact factor: 6.982