Association between APOE epsilon4 allele and increased expression of CD95 on T cells from patients with Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, characterized by progressive impairment of cognitive functions. AD has a strong and complex genetic etiology, and multiple genes, acting independently and/or interacting, likely to influence the risk of developing AD. To test whether the expression of Fas receptor is upregulated in peripheral blood T lymphocytes and whether or not it correlates with APOE genotypes, 88 patients with AD and 24 normal individuals as controls were included in this study. T lymphocytes from patients as opposed to controls did undergo DNA fragmentation after in vitro exposure to IgM anti-Fas. In addition, several activation markers (CD25, HLA-DR, and CD45R0) were increased after 72 h in culture with respect to the controls, and Fas expression was also significantly different from the control group (p < 0.01). Reverse transcription PCR for Fas mRNA yielded the same results. T cells from both patients and controls showed upregulation of Fas receptor expression after in vitro anti-CD3 stimulation. Co-culture experiments with interleukin-4 downmodulated surface Fas receptor expression on T cells from patients and at a lesser extent in the control group. AD patients with the APOE allele 4 showed an increased expression of CD95 (53% ± 6) with respect to APOE allele 3 (38% ± 4). The control group showed a 22% ± 3 (allele 4) and 31% ± 5 (allele 3), respectively. Hyperexpression of Fas mRNA and surface Fas receptor on CD45RO + T lymphocytes may explain the occurrence of inflammatory cellular infiltrates in the CNS of AD patients.