Neurofilament as a blood marker for diagnosis and monitoring of primary progressive aphasias.
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 Aβ1-42achieved 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.


METHODS
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.
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.
Petra
P
Steinacker
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.
Elisa
E
Semler
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.
Sarah
S
Anderl-Straub
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.
Janine
J
Diehl-Schmid
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.
Matthias L
ML
Schroeter
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.
Ingo
I
Uttner
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.
Hans
H
Foerstl
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.
Bernhard
B
Landwehrmeyer
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.
Christine A F
CA
von Arnim
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.
Jan
J
Kassubek
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.
Patrick
P
Oeckl
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.
Hans-Jürgen
HJ
Huppertz
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.
Klaus
K
Fassbender
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.
Klaus
K
Fliessbach
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.
Johannes
J
Prudlo
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.
Carola
C
Roßmeier
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.
Johannes
J
Kornhuber
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.
Anja
A
Schneider
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.
Alexander E
AE
Volk
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.
Martin
M
Lauer
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.
Adrian
A
Danek
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.
Albert C
AC
Ludolph
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.
Markus
M
Otto
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid; D018888:Aphasia, Primary Progressive / Q000097:blood* / Q000000981:diagnostic imaging; D001284:Atrophy / Q000000981:diagnostic imaging / Q000473:pathology; D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000097:blood* / Q000134:cerebrospinal fluid; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid; D012372:ROC Curve; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016900:Neurofilament Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C044882:neurofilament protein L; D016875:tau Proteins