NOTCH3 cysteine variants alter the white matter lesion-brain volume link in the general population

White matter hyperintensities on brain magnetic resonance imaging are established markers of cerebral small vessel disease and typically associate inversely with brain volume in the general population, reflecting irreversible tissue loss. In Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, a monogenic small vessel disease caused by NOTCH3 cysteine-altering mutations, white matter hyperintensities may instead reflect tissue water accumulation and perivascular space dilation rather than net structural damage. Whether this distinct pathophysiological rel

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