SVIP in plasma: a candidate blood-based biomarker for early detection of amnestic mild cognitive impairment

Amnestic mild cognitive impairment (aMCI) represents a critical clinical window for early intervention in Alzheimer's disease (AD). Identifying readily detectable, high-abundance plasma biomarkers for aMCI remains clinically important. Overexpression of Valosin-Containing Protein (VCP) has been shown to enhance autophagy and reduce tau levels in AD animal models. Notably, VCP, with a molecular weight of 90 kDa, typically assembles into hexamers, which is hypothesized to restrict its ability to cross the blood-brain barrier even under neurodegenerative conditions. In contrast, the small VCP-interacting protein (SVIP), with a molecular weight of only 9 kDa, interacts with VCP to maintain the dynamic stability of autophagosomes within cells. Therefore, we aim to explore plasma SVIP as a peripheral blood biomarker for aMCI and assess whether it can outperform VCP in detecting aMCI.

This was a retrospective study based on the STAR (Shenzhen Multi-modal Aging Research) cohort. Participants were recruited as a convenience sample. Eighty-four participants (44 cognitively unimpaired [CU], 40 aMCI) were included, with diagnostic classification based on standardized clinical and neuropsychological criteria. Plasma levels of SVIP and VCP were measured using deep plasma proteomics enriched with biofunctional magnetic beads. Diagnostic performance was evaluated using Receiver Operating Characteristic (ROC) analysis and DeLong's test. This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200066700).

Compared to the CU group, the aMCI group showed significantly decreased SVIP (p < 0.001), while no significant difference was observed in VCP levels (p = 0.823). The area under the curve (AUC) of SVIP in detecting aMCI was 0.836 (95% CI: 0.739 to 0.908), significantly higher than VCP [AUC = 0.513 (95% CI: 0.401 to 0.624)] (p < 0.0001, DeLong's test).

Plasma SVIP demonstrates significantly higher diagnostic accuracy than VCP for the detection of aMCI, suggesting its potential as a candidate blood-based biomarker pending large-scale pathophysiological validation.