Plasma p-tau181 and GFAP reflect 7T MR-derived changes in Alzheimer's disease: A longitudinal study of structural and functional MRI and MRS

Laura Göschel; Andrea Dell'Orco; Ariane Fillmer; Semiha Aydin; Bernd Ittermann; Layla Riemann; Sylvain Lehmann; Stefan Cano; Jeanette Melin; Leslie Pendrill; Patty L Hoede; Charlotte E Teunissen; Claudia Schwarz; Ulrike Grittner; Péter Körtvélyessy; Agnes Flöel

doi:10.1002/alz.14318

Plasma p-tau181 and GFAP reflect 7T MR-derived changes in Alzheimer's disease: A longitudinal study of structural and functional MRI and MRS

Alzheimers Dement. 2024 Nov 19. doi: 10.1002/alz.14318. Online ahead of print.

Authors

Laura Göschel^{1

2}, Andrea Dell'Orco^{1

2

3

4}, Ariane Fillmer³, Semiha Aydin³, Bernd Ittermann³, Layla Riemann^{3

5}, Sylvain Lehmann⁶, Stefan Cano⁷, Jeanette Melin⁸, Leslie Pendrill⁸, Patty L Hoede⁹, Charlotte E Teunissen⁹, Claudia Schwarz^{1

2

10}, Ulrike Grittner¹¹, Péter Körtvélyessy^{1

12}, Agnes Flöel^{10

13}

Affiliations

¹ Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
² Neuroscience Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³ Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Berlin, Germany.
⁴ Department of Neuroradiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁵ Institute for Applied Medical Informatics, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
⁶ LBPC-PPC, Université de Montpellier, INM INSERM, IRMB CHU de Montpellier, Montpellier, France.
⁷ Modus Outcomes Ltd, Cheltenham, UK.
⁸ Division Safety and Transport, Division Measurement Science and Technology, RISE, Research Institutes of Sweden, Gothenburg, Sweden.
⁹ Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
¹⁰ Department of Neurology, University Medicine Greifswald, Greifswald, Germany.
¹¹ Institute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹² German Center for Neurodegenerative Diseases (DZNE), Standort Magdeburg, Magdeburg, Germany.
¹³ German Center for Neurodegenerative Diseases (DZNE), Standort Rostock/Greifswald, Greifswald, Germany.

PMID: 39558898
DOI: 10.1002/alz.14318

Abstract

Background: Associations between longitudinal changes of plasma biomarkers and cerebral magnetic resonance (MR)-derived measurements in Alzheimer's disease (AD) remain unclear.

Methods: In a study population (n = 127) of healthy older adults and patients within the AD continuum, we examined associations between longitudinal plasma amyloid beta 42/40 ratio, tau phosphorylated at threonine 181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and 7T structural and functional MR imaging and spectroscopy using linear mixed models.

Results: Increases in both p-tau181 and GFAP showed the strongest associations to 7T MR-derived measurements, particularly with decreasing parietal cortical thickness, decreasing connectivity of the salience network, and increasing neuroinflammation as determined by MR spectroscopy (MRS) myo-inositol.

Discussion: Both plasma p-tau181 and GFAP appear to reflect disease progression, as indicated by 7T MR-derived brain changes which are not limited to areas known to be affected by tau pathology and neuroinflammation measured by MRS myo-inositol, respectively.

Highlights: This study leverages high-resolution 7T magnetic resonance (MR) imaging and MR spectroscopy (MRS) for Alzheimer's disease (AD) plasma biomarker insights. Tau phosphorylated at threonine 181 (p-tau181) and glial fibrillary acidic protein (GFAP) showed the largest changes over time, particularly in the AD group. p-tau181 and GFAP are robust in reflecting 7T MR-based changes in AD. The strongest associations were for frontal/parietal MR changes and MRS neuroinflammation.

Keywords: 7 Tesla; Alzheimer's disease; NeuroMET Memory Metric; amyloid beta 42/40; blood‐based biomarkers; functional magnetic resonance imaging; glial fibrillary acidic protein; magnetic resonance imaging; magnetic resonance spectroscopy; memory; mild cognitive impairment; neurofilament light chain; plasma biomarkers; subjective cognitive decline; tau phosphorylated at threonine 181.

Abstract

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