A biochemical screen performed with plasma of patients affected type 2 diabetes mellitus (T2DM, n=109), Alzheimer’s disease (AD, N=114)or AD-T2DM (n=116) has recently shown that the activities of the β- galactosidase (β-gal) and β-hexosaminidase (β-hex) may be used to monitor AD progression, especially in T2DM patients (Tiribuzi R. et al. J Alz Dis. 2010, M. 10-025). To better understand the relevance of lisosomal enzymes in AD and AD-T2DM, we expanded the screen to include lymphocytes, monocytes and CD34+ hematopoietic Stem Cells. The analysis of lysosomal hydrolase and proteases revealed that β-gal, β-hex and α-man activities were marhedly lower in lymphocytes and monocytes from AD and AD-T2DM patients, with a trend that correlated with changes in gene expression and alterations of isoenzyme profiles. Furthermore, cells from T2DM displayed down-regulated levels of cathepsin S and B. Notably, immunoblots revealed that mature forms of cathepsin S and D were exclusively detected in CD34+ HSCs from AD patients, whilke only precursor forms were observed in CD34+ HSCs from control subjects (n=122). These results point to phenotypically-regulated mechanism underlying the expression of lysosomal enzymes. The elucidation of these mechanisms may reveal novel insights into the biochemical wiring implicated in the connection between T2DM and AD.
Lysosomal hydrolases in Alzheimers and type 2 diabetes mellitus patients
TIRIBUZI, ROBERTO;ORLACCHIO, Aldo;CRISPOLTONI, LUCIA;PORCELLATI, Serena;DATTI, Alessandro;MARTINO, Sabata;
2010
Abstract
A biochemical screen performed with plasma of patients affected type 2 diabetes mellitus (T2DM, n=109), Alzheimer’s disease (AD, N=114)or AD-T2DM (n=116) has recently shown that the activities of the β- galactosidase (β-gal) and β-hexosaminidase (β-hex) may be used to monitor AD progression, especially in T2DM patients (Tiribuzi R. et al. J Alz Dis. 2010, M. 10-025). To better understand the relevance of lisosomal enzymes in AD and AD-T2DM, we expanded the screen to include lymphocytes, monocytes and CD34+ hematopoietic Stem Cells. The analysis of lysosomal hydrolase and proteases revealed that β-gal, β-hex and α-man activities were marhedly lower in lymphocytes and monocytes from AD and AD-T2DM patients, with a trend that correlated with changes in gene expression and alterations of isoenzyme profiles. Furthermore, cells from T2DM displayed down-regulated levels of cathepsin S and B. Notably, immunoblots revealed that mature forms of cathepsin S and D were exclusively detected in CD34+ HSCs from AD patients, whilke only precursor forms were observed in CD34+ HSCs from control subjects (n=122). These results point to phenotypically-regulated mechanism underlying the expression of lysosomal enzymes. The elucidation of these mechanisms may reveal novel insights into the biochemical wiring implicated in the connection between T2DM and AD.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
