Background: Cerebral small vessel disease (SVD) is an important cause of stroke and
vascular cognitive impairment (VCI), leading to subcortical ischemic vascular dementia. As a hereditary
form of SVD with early onset, cerebral autosomal dominant arteriopathy with subcortical
infarcts and leukoencephalopathy (CADASIL) represents a pure form of SVD and may thus serve
as a model disease for SVD. To date, underlying molecular mechanisms linking vascular pathology
and subsequent neuronal damage in SVD are incompletely understood.
Objective: We performed comparative transcriptional profiling microarray and proteomic analyses
on post-mortem frontal lobe specimen from 2 CADASIL patients and 5 non neurologically diseased
controls in order to identify dysregulated pathways potentially involved in the development
of tissue damage in CADASIL.
Methods: Transcriptional microarray analysis of material extracted from frontal grey and white
matter (WM) identified subsets of up- or down-regulated genes enriched into biological pathways
mostly in WM areas. Proteomic analysis of these regions also highlighted cellular processes identified
by dysregulated proteins.
Results: Discrepancies between proteomic and transcriptomic data were observed, but a number of
pathways were commonly associated with genes and corresponding proteins, such as: “ribosome”
identified by upregulated genes and proteins in frontal cortex or “spliceosome” associated with
down-regulated genes and proteins in frontal WM.
Conclusion: This latter finding suggests that defective expression of spliceosomal components
may alter widespread splicing profile, potentially inducing expression abnormalities that could
contribute to cerebral WM damage in CADASIL.