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Mechanism by which GOM deposits precipitate ischemic stroke in CADASIL

Determine the pathophysiological mechanism by which Granular Osmiophilic Material (GOM) deposits associated with NOTCH3 ectodomain accumulation lead to ischemic stroke in patients with CADASIL.

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Background

Granular Osmiophilic Material (GOM) deposits are a hallmark pathological feature of CADASIL and are associated with deposition of the NOTCH3 ectodomain in cerebral arterioles. Despite clear evidence of vascular alterations, including vessel wall thickening and reduced lumen diameter, the causal pathway from GOM deposition to ischemic stroke is not defined.

Understanding this mechanism is central to guiding disease-modifying treatments aimed at preventing stroke in CADASIL, beyond symptomatic management.

References

It is still unclear how GOM deposits result in ischemic stroke.

— Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL): Immunotherapy and Cell Therapy approaches (2506.09293 - Haile et al., 10 Jun 2025) in Mechanism of Disease