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The pericyte: A critical cell in the pathogenesis of CADASIL

Marie-Magdeleine Ruchoux1, Raj N Kalaria2, Gustavo C Román3

  • 1Former researcher, Université d'Artois, Blood-Brain-Barrier Laboratory Lens France, Former advisor, Alzheimer's Clinic Methodist Neurological Institute, Houston TX, USA.

Cerebral Circulation - Cognition and Behavior
|December 24, 2021
PubMed

Insights

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic small vessel disease. Pericyte damage in CADASIL may drive disease progression and offers new therapeutic targets.

Area of Science:

  • Neurology
  • Genetics
  • Vascular Biology

Background:

  • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small vessel disease.
  • It presents with migraines, cognitive decline, and neurological deficits due to NOTCH3 gene mutations.
  • CADASIL invariably leads to cognitive impairment and subcortical dementia with age.

Purpose of the Study:

  • To investigate the role of pericytes in CADASIL pathogenesis.
  • To explore novel therapeutic strategies targeting pericyte dysfunction.
  • To elucidate the mechanisms underlying cerebral small vessel diseases.

Main Methods:

  • Comprehensive review of morphological lesions in cerebral arteries, veins, and capillaries in CADASIL patients.
  • Analysis of pericyte-endothelial interactions and pericyte secretory functions.
  • Evaluation of pericyte-mediated effects on microvascular permeability and cerebral venous function.

Main Results:

  • Pericyte damage or deficiency is identified as a key feature in CADASIL pathogenesis.
  • Pericyte dysfunction affects endothelial interactions, leading to stroke injury and vasomotor disturbances.
  • Pericyte-mediated venous insufficiency may cause white matter lesions and Virchow-Robin space dilatation.

Conclusions:

  • Pericytes play a central role in CADASIL pathology, impacting microcirculation and blood-brain barrier integrity.
  • Targeting pericyte dysfunction presents a promising avenue for CADASIL treatment.
  • Understanding pericyte roles can advance the study of other small vessel diseases and vascular dementia.

Keywords:
Alzheimer diseaseBlood-brain barrierCADASILCerebral blood flowEndotheliumNOTCH3PericyteSubcortical vascular dementiaVascular smooth muscle cell

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