The pericyte: A critical cell in the pathogenesis of CADASIL.
Level 5 - mechanism / opinion, no new human data
Narrative review and mechanistic hypothesis paper with no new empirical human data.
PubMed 34950895 · doi:10.1016/j.cccb.2021.100031
What was done
The authors conducted a narrative review of morphological lesions across cerebral arteries, veins, and capillaries in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary small vessel disease caused by *NOTCH3* mutations.
What was found
No quantitative findings or empirical metrics are reported in the abstract. Based on reviewed structural evidence, the authors hypothesize that pericyte deficiency across arterioles and capillaries disrupts pericyte-endothelial signaling, increases microvascular blood-brain barrier permeability, contributes to delayed glial and neuronal death, and causes venous insufficiency linked to white matter lesions and dilated Virchow-Robin spaces.
Why it matters
Shifting the pathogenic paradigm of CADASIL to include microvascular and venous pericytes alongside arterial smooth muscle cells provides a mechanistic framework to identify novel therapeutic targets for hereditary and sporadic subcortical vascular dementias.
Limits
The paper is a narrative synthesis of existing literature rather than a systematic review or primary empirical study. No quantitative data, sample sizes, or study search parameters are reported in the abstract. The proposed pathogenic mechanisms represent theoretical inferences requiring prospective experimental and clinical validation.
Cited by
- supports CADASIL involves NOTCH3 protein aggregates in pericytes and vascular smooth muscle cells, leading to severe white matter disease and cognitive decline beginning around age 30 to 40.