In this presentation, Marcos Costa discussed the significant advancements in genetic association studies over the past decade, which have identified numerous genetic risk factors for diseases, particularly focusing on neuronal dysfunction and disease pathogenesis. Costa emphasised the need for a multidisciplinary approach, combining bioinformatics, neurobiology, bioengineering, neurophysiology, and clinical science to move from genetic landscapes to understanding disease mechanisms.
One of the key points highlighted was the role of the BIN1 gene in Alzheimer's disease. Costa explained that BIN1 is significantly associated with Alzheimer's disease risk, and its deletion leads to changes in neuronal activity, contributing to disease progression. He also discussed the interaction between BIN1 and the L-type calcium channel Cav1.2, noting that the deletion of BIN1 results in hyperactive and desynchronised neurons.
Costa also addressed the roles of PTK2B and PLC Gamma 2 genes in Alzheimer's disease. PTK2B is linked to tau phosphorylation and neuronal electrical properties, while PLC Gamma 2 is associated with both healthy ageing and Alzheimer's disease risk. He explained that the deletion or reduction of PTK2B expression leads to increased tau phosphorylation and changes in neuronal electrical activity. Similarly, the reduction of PLC Gamma 2 expression affects neuronal properties and increases the production of amyloid-beta and tau phosphorylation.
Furthermore, Costa explored the role of microglia, a type of glial cell, in Alzheimer's disease. He demonstrated that genetic mutations in microglia can affect neuronal properties and contribute to disease pathogenesis. By removing BIN1 from microglia in a mouse model, Costa showed that this led to changes in astrocytes and neurons, suggesting that microglial mutations could indirectly affect neuronal function.
In conclusion, Costa's presentation provided a comprehensive overview of the genetic factors, multidisciplinary approaches, and the roles of specific genes and cell types in understanding and treating diseases, particularly Alzheimer's disease.
