Association of GLOD4 with Alzheimers Disease in Humans and Mice
Glyoxylase domain containing protein (GLOD4) is associated with Alzheimers disease (AD). We quantified GLOD4 in human AD brains, mouse AD model, and neuroblastoma N2a-APPswe cells. We found that GLOD4 was downregulated in human AD patients compared to non-AD controls. Glod4 was similarly downregulated in Blmh-/-5xFAD mouse model of AD. Downregulated Glod4 was associated with elevated A{beta} and worsened memory/sensorimotor performance in Blmh-/-5xFAD mice. Glod4 depletion in N2a-APPswe cells upregulated A{beta}PP and downregulated autophagy-related Atg5 and p62 genes. These findings suggest that Glod4 interacts with A{beta}PP and the autophagy pathway, disruption of these interactions leads to A{beta} accumulation and cognitive/neurosensory deficits.