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

  • Lea Hüper
  • Petra Steinacker
  • Maryna Polyakova
  • Karsten Mueller
  • Jannis Godulla
  • Sabine Herzig
  • Adrian Danek
  • Annerose Engel
  • Janine Diehl-Schmid
  • Joseph Classen
  • Klaus Fassbender
  • Klaus Fliessbach
  • Holger Jahn
  • Jan Kassubek
  • Johannes Kornhuber
  • Bernhard Landwehrmeyer
  • Martin Lauer
  • Hellmuth Obrig
  • Patrick Oeckl
  • Johannes Prudlo
  • Dorothee Saur
  • Sarah Anderl-Straub
  • Matthis Synofzik
  • Matias Wagner
  • Jens Wiltfang
  • Juliane Winkelmann
  • Alexander E Volk
  • FTLD Consortium Germany
  • Hans-Jürgen Huppertz
  • Markus Otto
  • Matthias L Schroeter

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.

Bibliographical data

Original languageEnglish
ISSN1552-5260
DOIs
Publication statusPublished - 07.2024

Comment Deanary

© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

PubMed 38865340