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学術論文

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

MPS-Authors

Hüper,  Lea
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Polyakova,  Maryna       
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Clinic for Cognitive Neurology, University of Leipzig, Germany;

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Mueller,  Karsten
Method and Development Group Neural Data Science and Statistical Computing, MPI for Human Cognitive and Brain Sciences, Max Planck Society;

Godulla,  Jannis
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Clinic for Cognitive Neurology, University of Leipzig, Germany;

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Engel,  Annerose
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Clinic for Cognitive Neurology, University of Leipzig, Germany;

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Obrig,  Hellmuth       
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Clinic for Cognitive Neurology, University of Leipzig, Germany;

Prudlo,  Johannes
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Department of Neurology, University Medicine Rostock, Germany;

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Schroeter,  Matthias L.       
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;
Clinic for Cognitive Neurology, University of Leipzig, Germany;

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フルテキスト (公開)

Hueper_2024.pdf
(出版社版), 7MB

付随資料 (公開)

Hueper_2024_Suppl.pdf
(付録資料), 2MB

引用

Hüper, L., Steinacker, P., Polyakova, M., Mueller, K., Godulla, J., Herzig, S., Danek, A., Engel, A., Diehl‐Schmid, J., Classen, J., Fassbender, K., Fliessbach, K., Jahn, H., Kassubek, J., Kornhuber, J., Landwehrmeyer, B., Lauer, M., Obrig, H., Oeckl, P., Prudlo, J., Saur, D., Anderl‐Straub, S., Synofzik, M., Wagner, M., Wiltfang, J., Winkelmann, J., Volk, A. E., FTLD Consortium Germany, Huppertz, H., Otto, M., & Schroeter, M. L. (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.


引用: https://hdl.handle.net/21.11116/0000-000F-6BF7-3
要旨
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.