Serum brain-derived tau in lacunar stroke and cerebral small vessel disease

Brain-derived tau (BD-tau) selectively quantifies tau of central nervous system origin in blood and has demonstrated strong correlations with infarct volume and functional outcome in general ischaemic stroke, but data in lacunar stroke and cerebral small vessel disease (CSVD) are lacking.

In a prospectively collected cohort of 101 lacunar stroke patients with an MRI-confirmed recent small subcortical infarct (RSSI) and 47 controls, we measured serum BD-tau using the HD-X SIMOA platform at baseline and 3 and 15 months after stroke. We examined associations of BD-tau with infarct size, chronic CSVD neuroimaging features (white matter hyperintensities [WMHs], lacunes, microbleeds, total SVD score), CSVD progression on follow-up MRI and functional outcome.

Baseline serum BD-tau was higher in RSSI patients than controls (median 9.54 [7.32-12.20] vs 7.75 [6.18-9.44] pg/mL; P = .003) and correlated with infarct diameter (rs = 0.222, P = 0.039). Brain-derived tau did not correlate with time from stroke symptom onset to blood sampling (rs = 0.150, P = .179). Brain-derived tau was not associated with chronic CSVD neuroimaging features (WMHs, lacunes, microbleeds, SVD score; all P > .05) at any timepoint. Longitudinally, BD-tau returned to control levels by 3 months (P = .374) and remained stable at 15 months (P = .985). Brain-derived tau was neither associated with new vascular MRI lesions on follow-up nor functional neurological outcome.

Serum BD-tau is elevated acutely in CSVD-related RSSI, correlates with infarct size and normalises by 3 months. Brain-derived tau was not associated with chronic CSVD neuroimaging features or disease progression, suggesting sensitivity to acute neuronal injury rather than chronic or progressive CSVD.