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  Neurofilaments and progranulin are related to atrophy in frontotemporal lobar degeneration – A transdiagnostic study cross‐validating atrophy and fluid biomarkers

Hüper, L., Steinacker, P., Polyakova, M., Mueller, K., Godulla, J., Herzig, S., et al. (2024). Neurofilaments and progranulin are related to atrophy in frontotemporal lobar degeneration – A transdiagnostic study cross‐validating atrophy and fluid biomarkers. Alzheimer's & Dementia. doi:10.1002/alz.13863.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000F-6BF7-3 Version Permalink: https://hdl.handle.net/21.11116/0000-000F-6BFB-F
Genre: Journal Article

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 Creators:
Hüper, Lea1, Author
Steinacker, Petra2, Author
Polyakova, Maryna1, 3, Author                 
Mueller, Karsten4, Author           
Godulla, Jannis1, 3, Author
Herzig, Sabine3, Author
Danek, Adrian5, Author
Engel, Annerose1, 3, Author           
Diehl‐Schmid, Janine6, 7, Author
Classen, Joseph8, Author
Fassbender, Klaus9, Author
Fliessbach, Klaus10, 11, Author
Jahn, Holger12, Author
Kassubek, Jan13, Author
Kornhuber, Johannes14, Author
Landwehrmeyer, Bernhard13, Author
Lauer, Martin15, Author
Obrig, Hellmuth1, 3, Author                 
Oeckl, Patrick11, 13, Author
Prudlo, Johannes1, 16, Author
Saur, Dorothee8, AuthorAnderl‐Straub, Sarah13, AuthorSynofzik, Matthis11, 17, AuthorWagner, Matias18, 19, AuthorWiltfang, Jens11, 20, 21, AuthorWinkelmann, Juliane19, AuthorVolk, Alexander E.22, AuthorFTLD Consortium Germany, Author              Huppertz, Hans‐Jürgen23, AuthorOtto, Markus2, 13, AuthorSchroeter, Matthias L.1, 3, Author                  more..
Affiliations:
1Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
2Department of Neurology, Martin Luther University Halle-Wittenberg, Germany, ou_persistent22              
3Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              
4Method and Development Group Neural Data Science and Statistical Computing, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_3282987              
5Department of Neurology, Ludwig Maximilians University Munich, Germany, ou_persistent22              
6Department of Psychiatry and Psychotherapy, TU Munich, Germany, ou_persistent22              
7Clinical Center for Psychiatry, Psychotherapy, Psychosomatic Medicine, Geriatrics and Neurology, kbo-Inn-Salzach-Klinikum, Wasserburg/Inn, Germany, ou_persistent22              
8Department of Neurology, University Hospital Leipzig, Germany, ou_persistent22              
9Department of Neurology, Saarland University Homburg, Germany, ou_persistent22              
10Department of Psychiatry and Psychotherapy, University Bonn, Germany, ou_persistent22              
11German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, ou_persistent22              
12Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Germany, ou_persistent22              
13Department of Neurology, Ulm University, Germany, ou_persistent22              
14Department of Psychiatry and Psychotherapy, University Clinic Erlangen, Germany, ou_persistent22              
15Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Germany, ou_persistent22              
16Department of Neurology, University Medicine Rostock, Germany, ou_persistent22              
17Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Eberhard Karls University Tübingen, Germany, ou_persistent22              
18School of Medicine and Health, Institute of Human Genetics, TU Munich, Germany, ou_persistent22              
19Institute of Neurogenomics, Helmholtz Center Munich, Germany, ou_persistent22              
20Department of Psychiatry and Psychotherapy, Georg August University, Göttingen, Germany, ou_persistent22              
21Neurosciences and Signaling Group, Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Portugal, ou_persistent22              
22Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Germany, ou_persistent22              
23Swiss Epilepsy Centre, Zurich, Switzerland, ou_persistent22              

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Free keywords: Amyloid; Atrophy; Fluid biomarkers; Frontotemporal dementia; Frontotemporal lobar degeneration; Magnetic resonance imaging; Neurofilaments; Phospho‐tau; Progranulin; Tau; Ubiquitin
 Abstract: Introduction: Frontotemporal lobar degeneration (FTLD) encompasses behavioral variant frontotemporal dementia (bvFTD), progressive supranuclear palsy, corticobasal syndrome/degeneration, and primary progressive aphasias (PPAs). We cross-validated fluid biomarkers and neuroimaging.

Methods: Seven fluid biomarkers from cerebrospinal fluid and serum were related to atrophy in 428 participants including these FTLD subtypes, logopenic variant PPA (lvPPA), Alzheimer's disease (AD), and healthy subjects. Atrophy was assessed by structural magnetic resonance imaging and atlas-based volumetry.

Results: FTLD subtypes, lvPPA, and AD showed specific profiles for neurofilament light chain, phosphorylated heavy chain, tau, phospho-tau, amyloid beta1-42 from serum/cerebrospinal fluid, and brain atrophy. Neurofilaments related to regional atrophy in bvFTD, whereas progranulin was associated with atrophy in semantic variant PPA. Ubiquitin showed no effects.

Discussion: Results specify biomarker and atrophy patterns in FTLD and AD supporting differential diagnosis. They identify neurofilaments and progranulin in interaction with structural imaging as promising candidates for monitoring disease progression and therapy.

Highlights: Study cross-validated neuroimaging and fluid biomarkers in dementia. Five kinds of frontotemporal lobar degeneration and two variants of Alzheimer's disease. Study identifies disease-specific fluid biomarker and atrophy profiles. Fluid biomarkers and atrophy interact in a disease-specific way. Neurofilaments and progranulin are proposed as biomarkers for diagnosis and therapy.

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Language(s): eng - English
 Dates: 2024-06-12
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1002/alz.13863
Other: online ahead of print
PMID: 38865340
 Degree: -

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Project name : -
Grant ID : SCHR 774/5-1
Funding program : -
Funding organization : German Research Foundation (DFG)
Project name : -
Grant ID : 01GI1007A
Funding program : -
Funding organization : German Federal Ministry of Education and Research (BMBF)

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Title: Alzheimer's & Dementia
  Other : Alzheimer's and Dementia
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Hoboken, New Jersey, USA : Wiley
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 1552-5279
CoNE: https://pure.mpg.de/cone/journals/resource/2352-8729