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. 2020 Jun 1;41(8):2004-2013.
doi: 10.1002/hbm.24925. Epub 2020 Jan 16.

Contribution of CSF biomarkers to early-onset Alzheimer's disease and frontotemporal dementia neuroimaging signatures

Neus Falgàs  1   2 , Mariona Ruiz-Peris  1   3 , Agnès Pérez-Millan  1   3 , Roser Sala-Llonch  3 , Anna Antonell  1 , Mircea Balasa  1   4 , Sergi Borrego-Écija  1 , Oscar Ramos-Campoy  1 , Josep Maria Augé  5 , Magdalena Castellví  1 , Adrià Tort-Merino  1 , Jaume Olives  1 , Guadalupe Fernández-Villullas  1 , Kaj Blennow  6   7 , Henrik Zetterberg  6   7   8   9 , Núria Bargalló  10 , Albert Lladó  1 , Raquel Sánchez-Valle  1
Affiliations

Contribution of CSF biomarkers to early-onset Alzheimer's disease and frontotemporal dementia neuroimaging signatures

Neus Falgàs et al. Hum Brain Mapp. .

Abstract

Prior studies have described distinct patterns of brain gray matter and white matter alterations in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), as well as differences in their cerebrospinal fluid (CSF) biomarkers profiles. We aim to investigate the relationship between early-onset AD (EOAD) and FTLD structural alterations and CSF biomarker levels. We included 138 subjects (64 EOAD, 26 FTLD, and 48 controls), all of them with a 3T MRI brain scan and CSF biomarkers available (the 42 amino acid-long form of the amyloid-beta protein [Aβ42], total-tau protein [T-tau], neurofilament light chain [NfL], neurogranin [Ng], and 14-3-3 levels). We used FreeSurfer and FSL to obtain cortical thickness (CTh) and fraction anisotropy (FA) maps. We studied group differences in CTh and FA and described the "AD signature" and "FTLD signature." We tested multiple regression models to find which CSF-biomarkers better explained each disease neuroimaging signature. CTh and FA maps corresponding to the AD and FTLD signatures were in accordance with previous literature. Multiple regression analyses showed that the biomarkers that better explained CTh values within the AD signature were Aβ and 14-3-3; whereas NfL and 14-3-3 levels explained CTh values within the FTLD signature. Similarly, NfL levels explained FA values in the FTLD signature. Ng levels were not predictive in any of the models. Biochemical markers contribute differently to structural (CTh and FA) changes typical of AD and FTLD.

Keywords: Alzheimer's disease; Frontotemporal Dementia; biological markers; magnetic resonance imaging.

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Conflict of interest statement

H.Z. has served at scientific advisory boards of Roche Diagnostics, Wave, Samumed and CogRx, has given lectures in symposia sponsored by Biogen and Alzecure, and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures‐based platform company at the University of Gothenburg (all outside the submitted work). K.B. has served as a consultant or at advisory boards for Alector, Biogen, CogRx, Lilly, MagQu, Novartis, and Roche Diagnostics, and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture‐based platform company at the University of Gothenburg, all unrelated to the work presented in this article. The other authors have nothing to disclose.

Figures

Figure 1
Figure 1
Group maps of Alzheimer's disease and frontotemporal lobar degeneration patients compared with CTR. (a) Voxel‐wise maps of fraction anisotropy differences, showing only significant regions (corrected p < .05) on the standard MNI template. (b) Vertex‐wise maps, showing differences in cortical thickness represented on the cortical surface (corrected p < .05)
Figure 2
Figure 2
(a) Patterns of structural alterations associated with Alzheimer's disease and Frontotemporal Dementia (frontotemporal lobar degeneration, FTLD) (disease signatures). (b) Relative importance (%) of each cerebrospinal fluid biomarker and age in each multiple regression model
Figure 3
Figure 3
Vertex‐wise maps of correlations between CTh and cerebrospinal fluid‐biomarkers in frontotemporal lobar degeneration subjects
Figure 4
Figure 4
Voxel‐wise maps of correlation between fraction anisotropy and cerebrospinal fluid‐biomarkers, studied separately for each group
See this image and copyright information in PMC

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