Changes in Expression Profiles Revealed by Transcriptomic Analysis in Peripheral Blood Mononuclear Cells of Alzheimer's Disease Patients

Autor(es)

Leandro, Giovana Silva ^[1] ; Evangelista, Adriane Feijo ^[2] ; Lobo, Romulo Reboucas ^[3] ; Xavier, Danilo Jordao ^[1] ; Moriguti, Julio Cesar ^[3] ; Sakamoto-Hojo, Elza Tiemi ^{[1, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Genet, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil

^[2] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Philosophy Sci & Letters Ribeirao Preto, Dept Biol, Ave Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF ALZHEIMER'S DISEASE; v. 66, n. 4, p. 1483-1495, 2018.
• Citações Web of Science: 0

Resumo

Alzheimer's disease (AD) is an age-related neurodegenerative pathology associated with accumulation of DNA damage. Inflammation and cell cycle alterations seem to be implicated in the pathogenesis of AD, although the molecular mechanisms have not been thoroughly elucidated to date. The aim of the present study was to evaluate whether peripheral blood mononuclear cells (PBMCs) of AD patients display alterations in gene expression profiles, focusing on finding markers that might improve the diagnosis of AD. Blood samples were collected from 22 AD patients and 13 healthy individuals to perform genome-wide mRNA expression. We found 593 differentially expressed genes in AD compared to controls, from which 428 were upregulated, and 165 were downregulated. By performing a gene set enrichment analysis, we observed pathways involved in inflammation, DNA damage response, cell cycle, and neuronal processes. Moreover, functional annotation analyses indicated that differentially expressed genes are strongly related to pathways associated with the cell cycle and the immune system. The results were compared with those of an independent study on hippocampus samples, and a number of genes in common between both studies were identified as potential peripheral biomarkers for AD, including DUSP1, FOS, SLC7A2, RGS1, GFAP, CCL2, ANGPTL4, and SSPN. Taken together, our results demonstrate that PBMCs of AD patients do present alterations in gene expression profiles, and these results are comparable to those previously reported in the literature for AD neurons, supporting the hypothesis that blood peripheral mononuclear cells express molecular changes that occur in the neurons of AD patients. (AU)

• Processo FAPESP: 12/07879-5 - Avaliação da eficiência dos mecanismos de reparo do DNA e expressão gênica em linfócitos de indivíduos com a Doença de Alzheimer
• Beneficiário: Giovana da Silva Leandro
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/09352-7 - Instabilidade genômica e vias de sinalização molecular envolvendo respostas a danos e reparo do DNA em doenças humanas
• Beneficiário: Elza Tiemi Sakamoto Hojo
• Modalidade de apoio: Auxílio à Pesquisa - Regular