title: Shorter telomeres in patients with cerebral autosomal dominant arteriopathy and leukoencephalopathy (CADASIL).
abstract: CADASIL is a hereditary systemic vasculopathy which affects mainly small cerebral arteries and is caused by mutations in the Notch3 gene. Misfolding of Notch3 is linked to endoplasmic reticulum stress and increased reactive oxygen species, which may result in dysfunction of endothelial cells, inflammation and ischemia. Oxidative stress and inflammation may induce a rapid telomere shortening in peripheral blood leukocytes (PBLs). The aim of this study was to assess the telomere length in PBLs from 29 patients with a genetic diagnosis of CADASIL by using a modified quantitative real-time polymerase chain reaction based assay. PBL telomere length was significantly shorter in CADASIL patients (T/S ratio = 0.17, 95% CI, 0.14-0.20) than in the controls (T/S ratio = 0.31, 95% CI, 0.27-0.35, t-test p < 0.001). Moreover, patients with functional dependence displayed shorter telomeres than those with functional independence (p = 0.039). Our data provide the first evidence that PBL telomere length is shortened in CADASIL disease, and this may be a systemic oxidative stress indicator in CADASIL patients, providing a possible biomarker of disease progression and for future therapeutic strategies.
authors: Division of Neurology, Mazzoni Hospital, ASUR ZT 13, Ascoli Piceno, Italy.
authors: Michele
authors: M
authors: Ragno
authors: Luigi
authors: L
authors: Pianese
authors: Michele
authors: M
authors: Pinelli
authors: Serena
authors: S
authors: Silvestri
authors: Gabriella
authors: G
authors: Cacchiò
authors: Fabio
authors: F
authors: Di Marzio
authors: Maria
authors: M
authors: Scarcella
authors: Francesco
authors: F
authors: Coretti
authors: Fabiana
authors: F
authors: Altamura
authors: Antonella
authors: A
authors: Monticelli
authors: Imma
authors: I
authors: Castaldo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D046589:CADASIL / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016615:Telomere / Q000378:metabolism*; D059506:Telomere Shortening