Diagnostic Performance of Cerebrospinal Fluid Neurofilament Light Chain and Soluble Amyloid- Protein Precursor in the Subcortical Small Vessel Type of Dementia

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-beta protein precursor alpha (sA beta PP alpha), sA beta PP beta, 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 theWald 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 sA beta PP beta independently separated SSVD from controls, and sA beta PP beta also distinguished SSVD from AD and mixed dementia. The combination of NFL and sA beta PP beta discriminated SSVD from controls with high accuracy (AUROC 0.903, 95% CI: 0.834-0.972). Additionally, sA beta PP beta combined with the core AD biomarkers (amyloid-(beta 42), 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 sA beta PP beta to separate SSVD from controls supports that SSVD is a specific diagnostic entity. Moreover, SSVD was distinguished from AD and mixed dementia using sA beta PP beta in combination with the core AD biomarkers.