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.
Lombardi
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EBIOTEC, Biotechnology Division, La Coruna, Spain. biotecnologia@ebiotec.com
Fernández-Novoa
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Etcheverria
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Seoane
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Cacabelos
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D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D058846:Antibodies, Monoclonal, Murine-Derived; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D053938:DNA Fragmentation; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001057:Apolipoproteins E; D012333:RNA, Messenger; C411023:anti-Fas monoclonal antibody; D019014:fas Receptor