caa a22 4500 467881863 CHVBK 20190327083733.0 cr unu---uuuuu 170328e20061101xx s 000 0 eng 10.1007/s00702-006-0481-y doi (NATIONALLICENCE)springer-10.1007/s00702-006-0481-y Apolipoprotein E epsilon 4 is associated with an increased vulnerability to cell death in Alzheimer's disease [Elektronische Daten] [C. Frey, A. Bonert, T. Kratzsch, G. Rexroth, W. Rösch, F. Müller-Spahn, K. Maurer, W. E. Müller, A. Eckert] Summary.: The presumption to suffer from Alzheimer's disease (AD) accelerates with aging. One important risk factor seems to be the isoform epsilon 4 of the apolipoprotein E gene (Apo ɛ4), which increases the risk to develop AD at an earlier age. Furthermore, convincing evidence is provided that apoptotic cell death mechanisms play an important role in neuronal cell death in AD. In the present study, we investigated whether abnormalities in apoptosis and caspase-3 activity can be found at the level of lymphocytes and a T cell subtype, CD4 T cells, from AD patients compared to aged sex- and ApoE genotype-matched non-demented controls. Under different experimental conditions (at baseline or after in vitro incubation in the presence of proapoptotic stimuli) increased levels of apoptosis and enhanced caspase-3 activity were detected in lymphocytes from AD patients. This difference was most pronounced in the CD4+ T cell subtype. Notably, we found a significant increase of apoptotic cells and caspase-3 activity in lymphocytes from AD patients bearing one or two alleles of the ApoE4 compared to non-E4 carriers. Again, these effects were strongest in CD4+ T cells. Circulating amyloid-beta (Aβ) levels did not differ between AD patients bearing ApoE4 and non-ApoE4 and age-matched controls. Therefore, it is likely that circulating Aβ is not responsible for the observed effects, which might rather reflect an ongoing systemic response in AD, e.g. an increase in CD95 expression. Springer-Verlag, 2006 Keywords: Apoptosis, lymphocyte, caspase-3, Alzheimer patients, amyloid-beta, CD95 nationallicence Frey C. Department of Pharmacology, Biocenter, University of Frankfurt, Germany aut Bonert A. Department of Pharmacology, Biocenter, University of Frankfurt, Germany aut Kratzsch T. Department of Psychiatry and Psychotherapy I, J. W. Goethe University of Frankfurt, Germany aut Rexroth G. Medical Clinic, Nordwest Hospital, Frankfurt, Germany aut Rösch W. Medical Clinic, Nordwest Hospital, Frankfurt, Germany aut Müller-Spahn F. Neurobiology Research Laboratory, Psychiatric University Clinic, Basel, Switzerland aut Maurer K. Department of Psychiatry and Psychotherapy I, J. W. Goethe University of Frankfurt, Germany aut Müller W. E. Department of Pharmacology, Biocenter, University of Frankfurt, Germany aut Eckert A. Department of Pharmacology, Biocenter, University of Frankfurt, Germany aut Journal of Neural Transmission Springer-Verlag 113/11(2006-11-01), 1753-1761 0300-9564 113:11<1753 2006 113 702 https://doi.org/10.1007/s00702-006-0481-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-006-0481-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Frey C. Department of Pharmacology, Biocenter, University of Frankfurt, Germany aut NATIONALLICENCE 700 1- Bonert A. Department of Pharmacology, Biocenter, University of Frankfurt, Germany aut NATIONALLICENCE 700 1- Kratzsch T. Department of Psychiatry and Psychotherapy I, J. W. Goethe University of Frankfurt, Germany aut NATIONALLICENCE 700 1- Rexroth G. Medical Clinic, Nordwest Hospital, Frankfurt, Germany aut NATIONALLICENCE 700 1- Rösch W. Medical Clinic, Nordwest Hospital, Frankfurt, Germany aut NATIONALLICENCE 700 1- Müller-Spahn F. Neurobiology Research Laboratory, Psychiatric University Clinic, Basel, Switzerland aut NATIONALLICENCE 700 1- Maurer K. Department of Psychiatry and Psychotherapy I, J. W. Goethe University of Frankfurt, Germany aut NATIONALLICENCE 700 1- Müller W. E. Department of Pharmacology, Biocenter, University of Frankfurt, Germany aut NATIONALLICENCE 700 1- Eckert A. Department of Pharmacology, Biocenter, University of Frankfurt, Germany aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer-Verlag 113/11(2006-11-01), 1753-1761 0300-9564 113:11<1753 2006 113 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer