Diagnostic Performance of Cerebrospinal Fluid Neurofilament Light Chain and Soluble Amyloid-ß Protein Precursor ß 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-ß protein precursor α (sAßPPα), sAßPPß, 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 sAßPPß independently separated SSVD from controls, and sAßPPß also distinguished SSVD from AD and mixed dementia. The combination of NFL and sAßPPß discriminated SSVD from controls with high accuracy (AUROC 0.903, 95% CI: 0.834-0.972). Additionally, sAßPPß combined with the core AD biomarkers (amyloid-ß42, 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 sAßPPß to separate SSVD from controls supports that SSVD is a specific diagnostic entity. Moreover, SSVD was distinguished from AD and mixed dementia using sAßPPß in combination with the core AD biomarkers.