Research progress on cerebral small vessel disease in 2024

In 2024， significant progress has been made globally in the research of cerebral small vessel disease （cSVD）， particularly in genetic mechanisms， clinical typing， biomarkers and treatment strategies. However， challenges remain in terms of pathological complexity， insufficient specificity of biomarkers， and limited therapeutic means. Protein aggregates containing both wild-type and mutant NOTCH3 are key drivers of arterial pathology in CADASIL. Research on the staging of NOTCH3-related cSVD severity demonstrated that CADASIL can be clinically divided into 5 stages and 9 phases. For acute cerebral infarction thrombolysis in CADASIL， the risk of intravenous thrombolysis-related hemorrhage is relatively low due to the small volume of cerebral infarction. Progress has also been made in blood-based biomarkers for cSVD. Regarding the imaging biomarkers of cSVD， perivascular spaces in the basal ganglia， water diffusion fraction， and DTI-ALPS independently promote the burden of cSVD and cognitive decline. In the field of cerebral amyloid angiopathy （CAA）， studies have shown that anxiety can exacerbate neutrophil NETosis and promote the progression of CAA， opening new avenues for research on the role of neuroinflammation exacerbated by negative emotions in the pathogenesis of cSVD. In CAA combined with Alzheimer’s disease （AD）， 289 proteins showed different levels in CAA （+） vessels of AD patients， with associations to increased collagen-containing extracellular matrix， reduced ribonucleoprotein complexes， and decreased BBB proteins. SGLT2 and SGLT1 inhibition plays a protective role in the development of cSVD. This review introduces the progress in both the basic and clinical research of cSVD in 2024.