PLD3 in Alzheimer's disease.

Rare coding variants in the phospholipase D3 (PLD3) gene, also known as HU-K4, have recently been identified to increase the risk for late-onset Alzheimer's disease (LOAD) by the whole exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large independent LOAD case-control data series. PLD3 is highly expressed in the brain, especially mainly in neurons, but at a lower level in almost all tissues. The level of PLD3 was found to be downregulated in Alzheimer's disease (AD) brains, which was negatively correlated with amyloid precursor protein (APP) and amyloid-β (Aβ) levels. These findings suggested that PLD3 might be involved in AD pathogenesis through APP processing. Here, we briefly summarize the biochemical properties of PLD3, review recent genetic and expression findings of PLD3 that related to AD, and also speculate on the possible roles of PLD3 in the progression of this disease. Based on the contributing effects of PLD3 in AD pathogenesis, targeting PLD3 may provide new opportunities for AD therapeutic strategies.