Axelsson Andrén, E;
Kettunen, P;
Bjerke, M;
Rolstad, S;
Zetterberg, H;
Blennow, K;
Wallin, A;
... Zhu, YC; + view all
(2023)
Diagnostic Performance of Cerebrospinal Fluid Neurofilament Light Chain and Soluble Amyloid-β Protein Precursor β in the Subcortical Small Vessel Type of Dementia.
Journal of Alzheimer's Disease
, 96
(4)
pp. 1515-1528.
10.3233/JAD-230680.
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Abstract
Background: The subcortical small vessel type of dementia (SSVD) is a common subtype of vascular dementia, but there is a lack of disease-specific cerebrospinal fluid (CSF) biomarkers. Objective: We investigated whether CSF concentrations of neurofilament light chain (NFL), soluble amyloid-β protein precursor α (sAβPPα), sAβPPβ, and CSF/serum albumin ratio could separate SSVD from healthy controls, Alzheimer's disease (AD), and mixed dementia (combined AD and SSVD). Methods: This was a mono-center study of patients with SSVD (n = 38), AD (n = 121), mixed dementia (n = 62), and controls (n = 96). The CSF biomarkers were measured using immunoassays, and their independent contribution to the separation between groups were evaluated using the Wald test. Then, the area under the receiver operating characteristics curve (AUROC) and 95% confidence intervals (CIs) were calculated. Results: Elevated neurofilament light chain (NFL) and decreased sAβPPβ independently separated SSVD from controls, and sAβPPβ also distinguished SSVD from AD and mixed dementia. The combination of NFL and sAβPPβ discriminated SSVD from controls with high accuracy (AUROC 0.903, 95% CI: 0.834-0.972). Additionally, sAβPPβ combined with the core AD biomarkers (amyloid-β42, total tau, and phosphorylated tau181) had a high ability to separate SSVD from AD (AUROC 0.886, 95% CI: 0.830-0.942) and mixed dementia (AUROC 0.903, 95% CI: 0.838-0.968). Conclusions: The high accuracy of NFL and sAβPPβ to separate SSVD from controls supports that SSVD is a specific diagnostic entity. Moreover, SSVD was distinguished from AD and mixed dementia using sAβPPβ in combination with the core AD biomarkers.
| Type: | Article |
|---|---|
| Title: | Diagnostic Performance of Cerebrospinal Fluid Neurofilament Light Chain and Soluble Amyloid-β Protein Precursor β in the Subcortical Small Vessel Type of Dementia |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3233/JAD-230680 |
| Publisher version: | http://dx.doi.org/10.3233/jad-230680 |
| Language: | English |
| Additional information: | © 2023 – The authors. Published by IOS Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0). |
| Keywords: | Alzheimer’s disease, biomarkers, cerebrospinal fluid, neurofilament light chain, soluble amyloid-β protein precursor β, subcortical small vessel type of dementia, Humans, Amyloid beta-Protein Precursor, Amyloid beta-Peptides, Mixed Dementias, Intermediate Filaments, tau Proteins, Alzheimer Disease, Dementia, Neurofilament Proteins, Biomarkers |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10184802 |
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