TY - JOUR
T1 - Increased caspase activation in peripheral blood mononuclear cells of patients with Alzheimer's disease
AU - Tacconi, Santina
AU - Perri, Roberta
AU - Balestrieri, Emanuela
AU - Grelli, Sandro
AU - Bernardini, Sergio
AU - Annichiarico, Roberta
AU - Mastino, Antonio
AU - Caltagirone, Carlo
AU - Macchi, Beatrice
PY - 2004/11
Y1 - 2004/11
N2 - In this study, we investigated whether alterations in the pattern of caspase activation could be found at the level of peripheral blood mononuclear cells (PBMCs) in patients with Alzheimer's disease (AD). The results showed that in experimental conditions resembling a physiological stimulation, there was a statistically significant increase in the enzymatic activity of caspase-3, caspase-8, and caspase-9 in PBMCs from a small, but well-characterized, cohort of sporadic AD patients compared to those from a comparable control group of aged adults (AA). This was accompanied by a parallel, early increase in the cleavage activity of the same caspases. The higher level of caspase activity in PBMCs from AD compared to AA was not associated with quantitative differences in cell subset profiles. Moreover, no increase in apoptosis level, in the same experimental conditions, was found in PBMCs from this cohort of AD patients compared to those from AA. Conversely, the higher proneness to caspase activation in PBMCs from AD patients in comparison with that from AA was associated with a higher proliferative response to PHA or CD3. These data show a new dysfunction in AD patients at the PBMCs level and suggest that increased proneness to caspase activation in lymphocytes could reflect an ongoing systemic response in neurodegenerative disease with pathogenetic implications.
AB - In this study, we investigated whether alterations in the pattern of caspase activation could be found at the level of peripheral blood mononuclear cells (PBMCs) in patients with Alzheimer's disease (AD). The results showed that in experimental conditions resembling a physiological stimulation, there was a statistically significant increase in the enzymatic activity of caspase-3, caspase-8, and caspase-9 in PBMCs from a small, but well-characterized, cohort of sporadic AD patients compared to those from a comparable control group of aged adults (AA). This was accompanied by a parallel, early increase in the cleavage activity of the same caspases. The higher level of caspase activity in PBMCs from AD compared to AA was not associated with quantitative differences in cell subset profiles. Moreover, no increase in apoptosis level, in the same experimental conditions, was found in PBMCs from this cohort of AD patients compared to those from AA. Conversely, the higher proneness to caspase activation in PBMCs from AD patients in comparison with that from AA was associated with a higher proliferative response to PHA or CD3. These data show a new dysfunction in AD patients at the PBMCs level and suggest that increased proneness to caspase activation in lymphocytes could reflect an ongoing systemic response in neurodegenerative disease with pathogenetic implications.
KW - Aging
KW - Alzheimer's disease
KW - Apoptosis
KW - Caspases
KW - Lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=5044220307&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=5044220307&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2004.07.009
DO - 10.1016/j.expneurol.2004.07.009
M3 - Article
C2 - 15473998
AN - SCOPUS:5044220307
VL - 190
SP - 254
EP - 262
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
IS - 1
ER -