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

2004; Thomson Reuters; Volume: 26; Issue: 7 Linguagem: Inglês

10.1358/mf.2004.26.7.863735

2013-0155

Valter Lombardi, L. Fernández‐Novoa, Ignacio Etcheverrı́a, Silvia Seoane, Ramón Cacabelos,

Aluminum toxicity and tolerance in plants and animals

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.