Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases
(2024) In Nature Communications 15(1).- Abstract
Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer’s disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing... (More)
Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer’s disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.
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- author
- Karlsson, Linda LU ; Vogel, Jacob LU ; Arvidsson, Ida LU ; Åström, Kalle LU ; Janelidze, Shorena LU ; Blennow, Kaj LU ; Palmqvist, Sebastian LU ; Stomrud, Erik LU ; Mattsson-Carlgren, Niklas LU and Hansson, Oskar LU
- organization
-
- Clinical Memory Research (research group)
- LU Profile Area: Proactive Ageing
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- SciLifeLab Site@Lund (research group)
- Computer Vision and Machine Learning (research group)
- eSSENCE: The e-Science Collaboration
- ELLIIT: the Linköping-Lund initiative on IT and mobile communication
- LTH Profile Area: AI and Digitalization
- LU Profile Area: Natural and Artificial Cognition
- Mathematical Imaging Group (research group)
- LTH Profile Area: Engineering Health
- LU Profile Area: Light and Materials
- LU Profile Area: Nature-based future solutions
- publishing date
- 2024-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 15
- issue
- 1
- article number
- 3676
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85191724484
- pmid:38693142
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-024-47971-5
- language
- English
- LU publication?
- yes
- id
- ed785bd7-5deb-4714-a6b8-4e4a4f33d9be
- date added to LUP
- 2024-07-22 15:56:47
- date last changed
- 2024-09-30 21:29:39
@article{ed785bd7-5deb-4714-a6b8-4e4a4f33d9be, abstract = {{<p>Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer’s disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.</p>}}, author = {{Karlsson, Linda and Vogel, Jacob and Arvidsson, Ida and Åström, Kalle and Janelidze, Shorena and Blennow, Kaj and Palmqvist, Sebastian and Stomrud, Erik and Mattsson-Carlgren, Niklas and Hansson, Oskar}}, issn = {{2041-1723}}, language = {{eng}}, number = {{1}}, publisher = {{Nature Publishing Group}}, series = {{Nature Communications}}, title = {{Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases}}, url = {{http://dx.doi.org/10.1038/s41467-024-47971-5}}, doi = {{10.1038/s41467-024-47971-5}}, volume = {{15}}, year = {{2024}}, }