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  Neurofilament as a blood marker for diagnosis and monitoring of primary progressive aphasias

Steinacker, P., Semler, E., Anderl-Straub, S., Diehl-Schmid, J., Schroeter, M. L., Uttner, I., et al. (2017). Neurofilament as a blood marker for diagnosis and monitoring of primary progressive aphasias. Neurology, 88(10), 961-969. doi:10.1212/WNL.0000000000003688.

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Steinacker, Petra1, Author
Semler, Elisa1, Author
Anderl-Straub, Sarah1, Author
Diehl-Schmid, Janine2, Author
Schroeter, Matthias L.3, 4, Author           
Uttner, Ingo1, Author
Foerstl, Hans2, Author
Landwehrmeyer, Bernhard1, Author
von Arnim, Christine A.F.1, Author
Kassubek, Jan1, Author
Oeckl, Patrick1, Author
Huppertz, Hans-Jürgen5, Author
Fassbender, Klaus6, Author
Fliessbach, Klaus7, Author
Prudlo, Johannes8, Author
Roßmeier, Carola2, Author
Kornhuber, Johannes9, Author
Schneider , Anja10, Author
Volk, Alexander E.11, Author
Lauer, Martin12, Author
Danek, Adrian13, AuthorLudolph, Albert C.1, AuthorOtto, Markus1, Author more..
Affiliations:
1Department of Neurology, Ulm University, Germany, ou_persistent22              
2Department of Psychiatry and Psychotherapy, TU Munich, Germany, ou_persistent22              
3Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              
4Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, Leipzig, DE, ou_634549              
5Swiss Epilepsy Centre, Zurich, Switzerland, ou_persistent22              
6Department of Neurology, Saarland University Homburg, Germany, ou_persistent22              
7Department of Psychiatry and Psychotherapy, University Bonn, Germany, ou_persistent22              
8Department of Neurology, University Medicine Rostock, Germany, ou_persistent22              
9Department of Psychology and Psychotherapy, Friedrich Alexander University Erlangen, Germany, ou_persistent22              
10Department of Psychiatry and Psychotherapy, Georg August University, Göttingen, Germany, ou_persistent22              
11Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Germany, ou_persistent22              
12Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Germany, ou_persistent22              
13Department of Neurology, Ludwig Maximilians University Munich, Germany, ou_persistent22              

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 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.

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Language(s): eng - English
 Dates: 2016-07-272016-12-142017-02-082017-03
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1212/WNL.0000000000003688
PMID: 28179468
Other: Epub 2017
 Degree: -

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Title: Neurology
Source Genre: Journal
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Publ. Info: Cleveland, Ohio [etc.] : Advanstar Communications [etc.]
Pages: - Volume / Issue: 88 (10) Sequence Number: - Start / End Page: 961 - 969 Identifier: ISSN: 0028-3878
CoNE: https://pure.mpg.de/cone/journals/resource/954925246073