Neurofilaments and progranulin are related to atrophy in frontotemporal lobar degeneration – A transdiagnostic study cross‐validating atrophy and fluid biomarkers-Reference-Cited by-同舟云学术

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

Published:2024-06-12 Issue:7 Volume:20 Page:4461-4475
ISSN:1552-5260
Container-title:Alzheimer's & Dementia
language:en
Short-container-title:Alzheimer's & Dementia

Author:

Hüper Lea¹,Steinacker Petra²,Polyakova Maryna¹³,Mueller Karsten¹,Godulla Jannis¹³,Herzig Sabine³,Danek Adrian⁴,Engel Annerose¹³,Diehl‐Schmid Janine⁵⁶,Classen Joseph⁷,Fassbender Klaus⁸,Fliessbach Klaus⁹¹⁰,Jahn Holger¹¹,Kassubek Jan¹²,Kornhuber Johannes¹³,Landwehrmeyer Bernhard¹²,Lauer Martin¹⁴,Obrig Hellmuth¹³,Oeckl Patrick¹⁰¹²,Prudlo Johannes¹⁰¹⁵,Saur Dorothee⁷,Anderl‐Straub Sarah¹²,Synofzik Matthis¹⁰¹⁶,Wagner Matias¹⁷¹⁸,Wiltfang Jens¹⁰¹⁹²⁰,Winkelmann Juliane¹⁸,Volk Alexander E.²¹, ,Huppertz Hans‐Jürgen²²,Otto Markus²¹²,Schroeter Matthias L.¹³

Affiliation:

1. Department of Neurology Max Planck Institute for Human Cognitive and Brain Sciences Leipzig Germany

2. Department of Neurology University Clinic Halle, Martin Luther University Halle‐Wittenberg Halle, Saale Germany

3. Clinic for Cognitive Neurology University Hospital Leipzig Leipzig Germany

4. Department of Neurology Ludwig Maximilians University Munich Munich Germany

5. Department of Psychiatry and Psychotherapy School of Medicine Technical University of Munich Munich Germany

6. kbo‐Inn‐Salzach‐Klinikum, Clinical Center for Psychiatry, Psychotherapy, Psychosomatic Medicine Geriatrics and Neurology Wasserburg/Inn Germany

7. Department for Neurology University Hospital Leipzig Leipzig Germany

8. Department of Neurology Saarland University Hospital Homburg Germany

9. Department of Psychiatry and Psychotherapy University Hospital Bonn Bonn Germany

10. German Center for Neurodegenerative Diseases (DZNE) Bonn Germany

11. Department of Psychiatry and Psychotherapy University Hospital Hamburg‐Eppendorf Hamburg Germany

12. Department of Neurology University of Ulm Ulm Germany

13. Department of Psychiatry and Psychotherapy University Hospital Erlangen Erlangen Germany

14. Department of Psychiatry and Psychotherapy University Hospital Würzburg Würzburg Germany

15. Department of Neurology University Medicine Rostock Rostock Germany

16. Department of Neurodegenerative Diseases Center of Neurology Hertie Institute for Clinical Brain Research Tübingen Germany

17. Institute of Human Genetics School of Medicine and Health Technical University Munich Munich Germany

18. Institute of Neurogenomics Helmholtz Center Munich Neuherberg Germany

19. Department of Psychiatry and Psychotherapy University Medical Center Göttingen (UMG) Göttingen Germany

20. Neurosciences and Signaling Group Department of Medical Sciences Institute of Biomedicine (iBiMED) University of Aveiro Aveiro Portugal

21. Institute of Human Genetics University Medical Center Hamburg‐Eppendorf Hamburg Germany

22. Swiss Epilepsy Clinic Klinik Lengg Zurich Switzerland

Abstract

AbstractINTRODUCTIONFrontotemporal 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.METHODSSeven 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.RESULTSFTLD 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.DISCUSSIONResults 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.

Funder

Deutsche Forschungsgemeinschaft

Sächsische Aufbaubank

Publisher

Wiley

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