Petra Steinacker1, Elisa Semler1, Sarah Anderl-Straub1, Janine Diehl-Schmid1, Matthias L Schroeter1, Ingo Uttner1, Hans Foerstl1, Bernhard Landwehrmeyer1, Christine A F von Arnim1, Jan Kassubek1, Patrick Oeckl1, Hans-Jürgen Huppertz1, Klaus Fassbender1, Klaus Fliessbach1, Johannes Prudlo1, Carola Roßmeier1, Johannes Kornhuber1, Anja Schneider1, Alexander E Volk1, Martin Lauer1, Adrian Danek1, Albert C Ludolph1, Markus Otto2. 1. From the Department of Neurology (P.S., E.S., S.A.-S., I.U., B.L., C.A.F.v.A., J. Kassubek, P.O., A.C.L., M.O.), University of Ulm; Department of Psychiatry and Psychotherapy (J.D.-S., H.F., C.R.), Technical University of Munich; Clinic for Cognitive Neurology (M.L.S.), University Clinic Leipzig and Max Planck Institute for Human Cognitive and Brain Sciences, Germany; Swiss Epilepsy Center (H.-J.H.), Zürich, Switzerland; Department of Neurology (K. Fassbender), Saarland University, Homburg; Department of Psychiatry and Psychotherapy (K. Fliessbach), University of Bonn and DZNE; Department of Neurology (J.P.), University of Rostock and German Center for Neurodegenerative Diseases; Department of Psychiatry and Psychotherapy (J. Kornhuber), Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen; Department of Psychiatry and Psychotherapy (A.S.), University of Göttingen; Institute of Human Genetics (A.E.V.), University Medical Center Hamburg-Eppendorf, Hamburg; Department of Psychiatry and Psychotherapy (M.L.), University of Würzburg; and Department of Neurology (A.D.), Ludwig-Maximilians-University Munich, Germany. 2. From the Department of Neurology (P.S., E.S., S.A.-S., I.U., B.L., C.A.F.v.A., J. Kassubek, P.O., A.C.L., M.O.), University of Ulm; Department of Psychiatry and Psychotherapy (J.D.-S., H.F., C.R.), Technical University of Munich; Clinic for Cognitive Neurology (M.L.S.), University Clinic Leipzig and Max Planck Institute for Human Cognitive and Brain Sciences, Germany; Swiss Epilepsy Center (H.-J.H.), Zürich, Switzerland; Department of Neurology (K. Fassbender), Saarland University, Homburg; Department of Psychiatry and Psychotherapy (K. Fliessbach), University of Bonn and DZNE; Department of Neurology (J.P.), University of Rostock and German Center for Neurodegenerative Diseases; Department of Psychiatry and Psychotherapy (J. Kornhuber), Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen; Department of Psychiatry and Psychotherapy (A.S.), University of Göttingen; Institute of Human Genetics (A.E.V.), University Medical Center Hamburg-Eppendorf, Hamburg; Department of Psychiatry and Psychotherapy (M.L.), University of Würzburg; and Department of Neurology (A.D.), Ludwig-Maximilians-University Munich, Germany. markus.otto@uni-ulm.de.
Abstract
OBJECTIVE: To assess the utility of serum neurofilament for diagnosis and monitoring of primary progressive aphasia (PPA) variants. METHODS: We investigated neurofilament light chain (NF-L) levels in blood of 99 patients with PPA (40 with nonfluent variant PPA [nfvPPA], 38 with semantic variant PPA [svPPA], 21 with logopenic variant PPA [lvPPA]) and compared diagnostic performance with that reached by CSF NF-L, phosphorylated neurofilament heavy chain (pNF-H), β-amyloid (Aβ1-42), tau, and phosphorylated tau. The longitudinal change of blood NF-L levels was measured and analyzed for correlation with functional decline and brain atrophy. RESULTS: Serum NF-L is increased in PPA compared to controls and discriminates between nfvPPA/svPPA and lvPPA with 81% sensitivity and 67% specificity (cutoff 31 pg/mL). CSF NF-L, pNF-H, tau, phosphorylated tau, and Aβ1-42 achieved similar performance, and pNF-H was the only marker for discrimination of nfvPPA from svPPA/lvPPA. In most patients with nfvPPA and svPPA, but not lvPPA, serum NF-L increased within follow-up. The increase correlated with functional decline and progression of atrophy of the left frontal lobe of all patients with PPAs and the right middle frontal gyrus of patients with nfvPPA and svPPA. CONCLUSIONS: Blood level of NF-L can aid the differential diagnosis of PPA variants, especially in combination with CSF pNF-H. Because serum NF-L correlates with functional decline and atrophy in the disease course, it qualifies as an objective disease status marker. Extended follow-up studies with cases of known neuropathology are imperative. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with PPA, blood levels of NF-L can distinguish the logopenic variant from the nonfluent/agrammatic and semantic variants.
OBJECTIVE: To assess the utility of serum neurofilament for diagnosis and monitoring of primary progressive aphasia (PPA) variants. METHODS: We investigated neurofilament light chain (NF-L) levels in blood of 99 patients with PPA (40 with nonfluent variant PPA [nfvPPA], 38 with semantic variant PPA [svPPA], 21 with logopenic variant PPA [lvPPA]) and compared diagnostic performance with that reached by CSF NF-L, phosphorylated neurofilament heavy chain (pNF-H), β-amyloid (Aβ1-42), tau, and phosphorylated tau. The longitudinal change of blood NF-L levels was measured and analyzed for correlation with functional decline and brain atrophy. RESULTS: Serum NF-L is increased in PPA compared to controls and discriminates between nfvPPA/svPPA and lvPPA with 81% sensitivity and 67% specificity (cutoff 31 pg/mL). CSF NF-L, pNF-H, tau, phosphorylated tau, and Aβ1-42 achieved similar performance, and pNF-H was the only marker for discrimination of nfvPPA from svPPA/lvPPA. In most patients with nfvPPA and svPPA, but not lvPPA, serum NF-L increased within follow-up. The increase correlated with functional decline and progression of atrophy of the left frontal lobe of all patients with PPAs and the right middle frontal gyrus of patients with nfvPPA and svPPA. CONCLUSIONS: Blood level of NF-L can aid the differential diagnosis of PPA variants, especially in combination with CSF pNF-H. Because serum NF-L correlates with functional decline and atrophy in the disease course, it qualifies as an objective disease status marker. Extended follow-up studies with cases of known neuropathology are imperative. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with PPA, blood levels of NF-L can distinguish the logopenic variant from the nonfluent/agrammatic and semantic variants.
Authors: Julio C Rojas; Jee Bang; Iryna V Lobach; Richard M Tsai; Gil D Rabinovici; Bruce L Miller; Adam L Boxer Journal: Neurology Date: 2017-12-27 Impact factor: 9.910
Authors: Thomas Gattringer; Daniela Pinter; Christian Enzinger; Thomas Seifert-Held; Markus Kneihsl; Simon Fandler; Alexander Pichler; Christian Barro; Svenya Gröbke; Margarete Voortman; Lukas Pirpamer; Edith Hofer; Stefan Ropele; Reinhold Schmidt; Jens Kuhle; Franz Fazekas; Michael Khalil Journal: Neurology Date: 2017-10-18 Impact factor: 9.910
Authors: Lauren M Byrne; Filipe B Rodrigues; Kaj Blennow; Alexandra Durr; Blair R Leavitt; Raymund A C Roos; Rachael I Scahill; Sarah J Tabrizi; Henrik Zetterberg; Douglas Langbehn; Edward J Wild Journal: Lancet Neurol Date: 2017-06-07 Impact factor: 44.182
Authors: Amanpreet K Cheema; Laura E Wiener; Rebecca B McNeil; Maria M Abreu; Travis Craddock; Mary A Fletcher; Drew A Helmer; J Wesson Ashford; Kimberly Sullivan; Nancy G Klimas Journal: Life Sci Date: 2021-07-10 Impact factor: 6.780
Authors: Ignacio Illán-Gala; Alberto Lleo; Anna Karydas; Adam M Staffaroni; Henrik Zetterberg; Rajeev Sivasankaran; Lea T Grinberg; Salvatore Spina; Joel H Kramer; Eliana M Ramos; Giovanni Coppola; Renaud La Joie; Gil D Rabinovici; David C Perry; Maria Luisa Gorno-Tempini; William W Seeley; Bruce L Miller; Howard J Rosen; Kaj Blennow; Adam L Boxer; Julio C Rojas Journal: Neurology Date: 2020-11-16 Impact factor: 11.800
Authors: Charlotte E Teunissen; Markus Otto; Sebastiaan Engelborghs; Sanna-Kaisa Herukka; Sylvain Lehmann; Piotr Lewczuk; Alberto Lleó; Armand Perret-Liaudet; Hayrettin Tumani; Martin R Turner; Marcel M Verbeek; Jens Wiltfang; Henrik Zetterberg; Lucilla Parnetti; Kaj Blennow Journal: Alzheimers Res Ther Date: 2018-03-15 Impact factor: 6.982