We found that the APOE ε4 allele is associated with a higher risk for PD-D. Gene-gene interaction analysis revealed that three significant gene-gene interactions, including BDNF and CLU, APOE and CR1, and DYRK1A and CD2AP increase the risk for PD.
The identification of hundreds of genes deregulated by DYRK1A overexpression and numerous cytosolic, cytoskeletal and nuclear proteins, including transcription factors, phosphorylated by DYRK1A, indicates that DYRK1A overexpression is central for the deregulation of multiple pathways in the developing and aging DS brain, with structural and functional alterations including mental retardation and dementia.