Increased caspase activation in peripheral blood mononuclear cells of patients with Alzheimer's disease.
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.
Tacconi
Santina
S
Department of Experimental Medicine and Biochemical Sciences, University Hospital of Tor Vergata, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
Perri
Roberta
R
Balestrieri
Emanuela
E
Grelli
Sandro
S
Bernardini
Sergio
S
Annichiarico
Roberta
R
Mastino
Antonio
A
Caltagirone
Carlo
C
Macchi
Beatrice
B
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000201:enzymology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D017209:Apoptosis / Q000187:drug effects; D017252:CD3 Complex / Q000494:pharmacology; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D015331:Cohort Studies; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D012016:Reference Values
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D017252:CD3 Complex; D010835:Phytohemagglutinins; C411023:anti-Fas monoclonal antibody; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases