Busca de biomarcadores para a doença de Alzheimer
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Data
2023-02-08
Autores
Almeida, Jucimara Ferreira Figueiredo
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Universidade Federal do Espírito Santo
Resumo
Alzheimer's disease (AD) is one of the most common forms of dementia in the population and currently in Brazil there are more than 1.2 million individuals with AD. In AD there is death of neurons and loss of synapses, inflammatory processes and brain atrophy caused by the formation of amyloid plaques and tangles of neurofibrils. In 98% of the cases, AD is sporadic, and the APOE gene acts as the most risk factor. The pathophysiological process of AD begins many years before clinically evident symptoms. In this sense, the identification of genetic biomarkers would allow for a less invasive, more accurate diagnosis with a more accessible value, in the same way it could be used as a marker of progression and response to treatment. Thus, the main objective of this work was to search for potential AD biomarkers by studying polymorphisms in the ABCA7 (rs3764650), CR1 (rs6656401), BIN1 (rs744373), CLU (rs11136000) and MS4A6A (rs610932) genes in a meta-analysis. In addition, an association study of the CASS4 (rs911159), TREM2 (rs75932628), CD2AP (rs9349407) and MS4A4E, (rs670139) gene variants and a combined risk study of the APOE (rs429358 and rs7412), BIN1 (rs744373) genes, ABCA7 (rs3764650) and CLU (rs11136000). The results of the meta-analysis validated the risk of BIN1, CR1, ABCA7 gene variants, as well as the protective effect of MS4A6A and CLU. In the combined risk study, the results suggest a risk effect for AD between APOE with CLU and APOE with the BIN1 gene. In the case-control study, there was a positive association of the rs911159 polymorphism of the CASS4 gene with Alzheimer's disease. These results, in addition to validating GWAS studies in a poorly studied population, such as the Brazilian population, were important to broaden the understanding of the disease and increase the diversity of populations studied in the world in genetic studies for AD. In addition, this work opens the way for new studies in search of early diagnostic biomarkers for sporadic Alzheimer's disease.
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Palavras-chave
Doença de Alzheimer Esporádica , Biomarcadores , GWAS , Genética