TY - JOUR
T1 - Differential blood-based biomarkers of subcortical and deep brain small vessel disease
AU - Hervella, Pablo
AU - Alonso-Alonso, Maria Luz
AU - Sampedro-Viana, Ana
AU - Rodríguez-Yáñez, Manuel
AU - López-Dequidt, Iria
AU - Pumar, José M.
AU - Ouro, Alberto
AU - Romaus-Sanjurjo, Daniel
AU - Campos, Francisco
AU - Sobrino, Tomás
AU - Castillo, José
AU - Leira, Yago
AU - Iglesias-Rey, Ramón
N1 - Publisher Copyright:
© The Author(s), 2024.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - Background: Cerebral small vessel disease is the most common cause of lacunar strokes (LS). Understanding LS pathogenesis is vital for predicting disease severity, prognosis, and developing therapies. Objectives: To research molecular profiles that differentiate LS in deep brain structures from those in subcortical white matter. Design: Prospective case–control study involving 120 patients with imaging-confirmed LS and a 120 control group. Methods: We examined the relationship between Alzheimer’s disease biomarkers [amyloid beta (Aβ1–40, Aβ1–42)], serum inflammatory marker (interleukin-6, IL-6), and endothelial dysfunction markers [soluble tumor necrosis factor-like weak inducer of apoptosis, and pentraxin-3 (sTWEAK, PTX3)] with respect to LS occurring in deep brain structures and subcortical white matter. In addition, we investigated links between LS, leukoaraiosis presence (white matter hyperintensities, WMHs), and functional outcomes at 3 months. Poor outcome was defined as a modified Rankin scale >2 at 3 months. Results: Significant differences were observed in levels of IL-6, PTX3, and sTWEAK between patients with deep lacunar infarcts and those with recent small subcortical infarcts (20.8 versus 15.6 pg/mL, p < 0.001; 7221.3 versus 4624.4 pg/mL, p < 0.0001; 2528.5 versus 1660.5 pg/mL, p = 0.001). Patients with poor outcomes at 3 months displayed notably higher concentrations of these biomarkers compared to those with good outcomes. By contrast, Aβ1–40 and Aβ1–42 were significantly lower in patients with deep LS (p < 0.0001). Aβ1–42 levels were significantly higher in patients with LS in subcortical white matter who had poor outcomes. WMH severity only showed a significant association with deep LS and correlated with sTWEAK (p < 0.0001). Conclusion: The pathophysiological mechanisms of lacunar infarcts in deep brain structures seem different from those in the subcortical white matter. As a result, specific therapeutic and preventive strategies should be explored.
AB - Background: Cerebral small vessel disease is the most common cause of lacunar strokes (LS). Understanding LS pathogenesis is vital for predicting disease severity, prognosis, and developing therapies. Objectives: To research molecular profiles that differentiate LS in deep brain structures from those in subcortical white matter. Design: Prospective case–control study involving 120 patients with imaging-confirmed LS and a 120 control group. Methods: We examined the relationship between Alzheimer’s disease biomarkers [amyloid beta (Aβ1–40, Aβ1–42)], serum inflammatory marker (interleukin-6, IL-6), and endothelial dysfunction markers [soluble tumor necrosis factor-like weak inducer of apoptosis, and pentraxin-3 (sTWEAK, PTX3)] with respect to LS occurring in deep brain structures and subcortical white matter. In addition, we investigated links between LS, leukoaraiosis presence (white matter hyperintensities, WMHs), and functional outcomes at 3 months. Poor outcome was defined as a modified Rankin scale >2 at 3 months. Results: Significant differences were observed in levels of IL-6, PTX3, and sTWEAK between patients with deep lacunar infarcts and those with recent small subcortical infarcts (20.8 versus 15.6 pg/mL, p < 0.001; 7221.3 versus 4624.4 pg/mL, p < 0.0001; 2528.5 versus 1660.5 pg/mL, p = 0.001). Patients with poor outcomes at 3 months displayed notably higher concentrations of these biomarkers compared to those with good outcomes. By contrast, Aβ1–40 and Aβ1–42 were significantly lower in patients with deep LS (p < 0.0001). Aβ1–42 levels were significantly higher in patients with LS in subcortical white matter who had poor outcomes. WMH severity only showed a significant association with deep LS and correlated with sTWEAK (p < 0.0001). Conclusion: The pathophysiological mechanisms of lacunar infarcts in deep brain structures seem different from those in the subcortical white matter. As a result, specific therapeutic and preventive strategies should be explored.
KW - cerebral small vessel disease
KW - ischemic stroke
KW - lacunar stroke
KW - leukoaraiosis
KW - white matter hyperintensities
UR - http://www.scopus.com/inward/record.url?scp=85195514783&partnerID=8YFLogxK
U2 - 10.1177/17562864241243274
DO - 10.1177/17562864241243274
M3 - Article
C2 - 38827243
AN - SCOPUS:85195514783
SN - 1756-2856
VL - 17
JO - Therapeutic Advances in Neurological Disorders
JF - Therapeutic Advances in Neurological Disorders
ER -