Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
Level 5 - mechanism / opinion, no new human data
Bench and animal research without human data.
PubMed 26312599 · doi:10.1002/ana.24512
What was done
Investigators evaluated 2-, 7-, and 12-month-old CADASIL mutant mice (TgNotch3(R169C)) and wild-type controls. They evaluated Notch3 aggregation in pericytes, pericyte capillary coverage, pericyte numbers, capillary density, blood-brain barrier integrity, astrocytic end-feet, and expression of astrocytic gap junction and endothelial adherens junction proteins via immunostaining and Western blot. Cerebrovascular CO2 reactivity was assessed using laser Doppler fluxmetry and in vivo microscopy.
What was found
Mutated Notch3 accumulated around pericytes and smooth muscle cells with increasing age. Notch3 aggregation was associated with a significant reduction in pericyte number and pericyte capillary coverage (p < 0.01), along with astrocytic end-feet detachment, plasma protein leakage, decreased endothelial adherens junction protein expression, and reduced microvascular reactivity to CO2. Smooth muscle cells were reported not to be affected by Notch3 accumulation. Exact numerical values and effect sizes were not provided in the abstract.
Why it matters
This work identifies pericytes as early cellular targets in CADASIL pathogenesis, linking pericyte degeneration directly to blood-brain barrier leakage and microvascular dysfunction.
Limits
The study was conducted entirely in a transgenic mouse model rather than human subjects. The abstract does not report the sample size (n), baseline quantitative values, effect sizes, or variance metrics.
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.