Contribution of CSF biomarkers to early‐onset Alzheimer's disease and frontotemporal dementia neuroimaging signatures
Open accessAbstract
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.
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- Authors
- Falgàs, N., Ruiz‐Peris, M., Pérez‐Millan, A., Sala‐Llonch, R., Antonell, A., Balasa, M., Borrego‐Écija, S., Ramos‐Campoy, O., Augé, J. M., Castellví, M., Tort‐Merino, A., Olives, J., Fernández‐Villullas, G., Blennow, K., Zetterberg, H., Bargalló, N., Lladó, A., & Sánchez‐Valle, R.
- Affiliations
- University of California, San Francisco (US)
- Fundació Clínic per a la Recerca Biomèdica (ES)
- Universitat de Barcelona (ES)
- Trinity College Dublin (IE)
- Biochemistry and Molecular Genetics Department, Hospital Clínic de Barcelona Barcelona Spain
- Sahlgrenska University Hospital (SE)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Corresponding author
- Sánchez‐Valle, Raquel
- ORCID
- Venue
- Human Brain Mapping
- Publisher
- Wiley
- Published
- 2020-01-16
- Volume
- 41
- Issue
- 8
- Pages
- 2004-2013
- ISSN
- 1065-9471 (ISSN-L)
- 1097-0193
- PMC
- PMC7267898
- OpenAlex
- W2998845095
- Cited by
- 32
- References
- 44
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 7 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 4
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Human Brain Mapping (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by-nc)
- UCL Discovery (University College London) (submittedVersion)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- Funders
- Forskningsrådet om Hälsa, Arbetsliv och Välfärd (2018‐02532)
- Generalitat de Catalunya (SLT002/16/00408, SLT008/18/00061, SLT002/16/00329)
- European Research Council (681712)
- Hjärnfonden (FO2017‐0243)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- early-onset Alzheimer's disease, frontotemporal lobar degeneration, cerebrospinal fluid biomarkers, cortical thickness, fractional anisotropy, amyloid-beta, tau protein, neurofilament light chain, neurogranin, gray matter alterations, white matter changes
- MeSH terms
- Alzheimer Disease, Cerebral Cortex, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins, Neurofilament Proteins, Age of Onset, 14-3-3 Proteins, Neurogranin, Diffusion Tensor Imaging, Frontotemporal Dementia, Neuroimaging
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