Markers of neural degeneration and regeneration in Down syndrome patients

On the trisomy Down syndrome Critical Region (DSCR1) is located the APP gene, which accelerates amyloid peptide protein (APP) expression leading to cerebral accumulation of APP-derived amyloid-beta peptides (Aβ) and age-dependent cognitive sequelae. Also DSCR1 attenuates endothelial cell proliferation and angiogenesis required for tissue repair. The aim of the present work is to determine markers of neural degeneration and regeneration in the blood of young and adolescent Down syndrome (DS) patients as well as controls. Markers of regeneration were measured in terms of circulating mononuclear cells expressing Nestin and CD34, while markers of degeneration were measured in terms of plasma Aβ42 and advanced glycation end products receptors (RAGES). Results showed a significant increase in plasma Aβ42 (20 ± 5.1 vs. 11.9 ± 3.4) and RAGES leucocytes mRNA relative expression (1.9 ± 0.2 vs. 1.1 ± 0.6) in adolescent DS patients compared to young DS. Both parameters were also significantly increased in DS compared to controls: Aβ42 (15.4 ± 5.9 vs. 12. 3 ± 4.5); RAGES (1.4 ± 0.5 vs. 0.7 ± 0.2). Nestin (5.2 ± 1.4 vs. 6.3 ± 0.6) and CD34 (52 ± 2.5 vs. 53 ± 4.7) were non-significantly lower in adolescent DS patients compared to young DS, but significantly lower in DS patients compared to controls: Nestin (6.3 ± 1.5 vs. 9 ± 4.4); CD34 (54 ± 3.4 vs. 60 ± 4.8). The significant decrease in the number of mononuclear cells bearing Nestin and CD34 markers accompanied by a significant increase in Aβ42 and RAGES indicate that degeneration in DS is an ongoing process, which is not counterbalanced by the regenerative mechanism.