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

被引：2

作者：

Hueper, Lea ^{[1
]}

Steinacker, Petra ^{[2
]}

Polyakova, Maryna ^{[1
,3
]}

Mueller, Karsten ^{[1
]}

Godulla, Jannis ^{[1
,3
]}

Herzig, Sabine ^{[3
]}

Danek, Adrian ^{[4
]}

Engel, Annerose ^{[1
,3
]}

Diehl-Schmid, Janine ^{[5
,6
]}

Classen, Joseph ^{[7
]}

Fassbender, Klaus ^{[8
]}

Fliessbach, Klaus ^{[9
,10
]}

Jahn, Holger ^{[11
]}

Kassubek, Jan ^{[12
]}

Kornhuber, Johannes ^{[13
]}

Landwehrmeyer, Bernhard ^{[12
]}

Lauer, Martin ^{[14
]}

Obrig, Hellmuth ^{[1
,3
]}

Oeckl, Patrick ^{[10
,12
]}

Prudlo, Johannes ^{[10
,15
]}

Saur, Dorothee ^{[7
]}

Anderl-Straub, Sarah ^{[12
]}

Synofzik, Matthis ^{[10
,16
]}

Wagner, Matias ^{[17
,18
]}

Wiltfang, Jens ^{[10
,19
,20
]}

Winkelmann, Juliane ^{[18
]}

Volk, Alexander E. ^{[21
]}

Huppertz, Hans-Juergen ^{[22
]}

Otto, Markus ^{[2
]}

Schroeter, Matthias L. ^{[1
,3
]}

机构：

[1] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Stephanstr 1A, D-04103 Leipzig, Germany

[2] Martin Luther Univ Halle Wittenberg, Univ Clin Halle, Dept Neurol, Halle, Saale, Germany

[3] Univ Hosp Leipzig, Clin Cognit Neurol, Leipzig, Germany

[4] Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany

[5] Tech Univ Munich, Sch Med, Dept Psychiat & Psychotherapy, Munich, Germany

[6] Kbo Inn Salzach Klinikum, Clin Ctr Psychiat Psychotherapy Psychosomat Med G, Wasserburg, Germany

[7] Univ Hosp Leipzig, Dept Neurol, Leipzig, Germany

[8] Saarland Univ Hosp, Dept Neurol, Homburg, Germany

[9] Univ Hosp Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany

[10] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany

[11] Univ Hosp Hamburg Eppendorf, Dept Psychiat & Psychotherapy, Hamburg, Germany

[12] Univ Ulm, Dept Neurol, Ulm, Germany

[13] Univ Hosp Erlangen, Dept Psychiat & Psychotherapy, Erlangen, Germany

[14] Univ Hosp Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany

[15] Univ Med Rostock, Dept Neurol, Rostock, Germany

[16] Hertie Inst Clin Brain Res, Ctr Neurol, Dept Neurodegenerat Dis, Tubingen, Germany

[17] Tech Univ Munich, Inst Human Genet, Sch Med & Hlth, Munich, Germany

[18] Helmholtz Ctr Munich, Inst Neurogenom, Neuherberg, Germany

[19] Univ Med Ctr Gottingen UMG, Dept Psychiat & Psychotherapy, Gottingen, Germany

[20] Univ Aveiro, Inst Biomed iBiMED, Dept Med Sci, Neurosci & Signaling Grp, Aveiro, Portugal

[21] Univ Med Ctr Hamburg Eppendorf, Inst Human Genet, Hamburg, Germany

[22] Klin Lengg, Swiss Epilepsy Clin, Zurich, Switzerland

来源：

ALZHEIMERS & DEMENTIA | 2024年 / 20卷 / 07期

关键词：

amyloid; atrophy; fluid biomarkers; frontotemporal dementia; frontotemporal lobar degeneration; magnetic resonance imaging; neurofilaments; phospho-tau; progranulin; tau; ubiquitin; CEREBROSPINAL-FLUID; PROBABILISTIC ATLAS; BEHAVIORAL VARIANT; TAU-PROTEIN; HUMAN BRAIN; NEURODEGENERATIVE DISEASES; ALZHEIMERS-DISEASE; LIGHT-CHAIN; LARGE-SCALE; DEMENTIA;

D O I：

10.1002/alz.13863

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

INTRODUCTIONFrontotemporal 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.

引用

页码：4461 / 4475

页数：15

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