Structural and functional connectivity in tau mutation carriers: from presymptomatic to symptomatic frontotemporal dementia

Bouzigues, Arabella ; Du, Vincent Le; Joulot, Matthieu; Peysson, Ninon; Houot, Marion; Béranger, Benoît; Russell, Lucy L.; Foster, Phoebe H.; Ferry‐Bolder, Eve; Swieten, John C. van; Jiskoot, Lize; Seelaar, Harro; Sanchez‐Valle, Raquel; Laforce, Robert; Graff, Caroline; Galimberti, Daniela; Vandenberghe, Rik; Mendonça, Alexandre de ; Tiraboschi, Pietro; Santana, Isabel; Gerhard, Alexander; Levin, Johannes ; Sorbi, Sandro; Otto, Markus; Bertoux, Maxime; Lebouvier, Thibaud; Ducharme, Simon; Butler, Chris R.; Ber, Isabelle Le; Finger, Elizabeth; Tartaglia, Maria Carmela; Masellis, Mario; Rowe, James B.; Synofzik, Matthis; Moreno, Fermin; Borroni, Barbara; Rohrer, Jonathan D. und Migliaccio, Raffaella (2025): Structural and functional connectivity in tau mutation carriers: from presymptomatic to symptomatic frontotemporal dementia. In: Alzheimer's & Dementia, Bd. 21, Nr. 7, e70367

Abstract

INTRODUCTION

Microtubule-associated protein tau (MAPT) mutations cause frontotemporal dementia (FTD), characterised by behavioural, language, and motor impairments due to brain connectivity disruptions. We investigated structural and functional connectivity in 86 mutation carriers and 272 controls to map connectivity changes at different disease stages.

METHODS

The CDR Dementia Staging Instrument plus National Alzheimer's Coordinating Center (NACC) Behaviour and Language domains (CDR plus NACC FTLD) stratified carriers into three groups: asymptomatic, prodromal, and symptomatic. We extracted measures of cortical thickness, white matter integrity, and functional connectivity, which were compared between each carrier group and controls using linear mixed models.

RESULTS

Early isolated functional disruptions in salience/visual networks were present in asymptomatic carriers, along with anterior cingulate gray matter reductions. In prodromal carriers, functional changes extended to other networks, with additional structural damage in temporal poles/cingulate.

DISCUSSION

This study shows that functional networks likely drive lifelong compensation for a genetically determined disease, manifesting clinically when structural damage reaches a critical threshold. This supports connectivity measures as potential biomarkers for MAPT-related neurodegeneration.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1552-5260
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198