PLD3 Gene Creates Risk of Alzheimer’s disease

A rare mutation in the phospholipase D3 protein is linked to Alzheimer’s disease that interferes with phospholipase D3 vital recycling function inside neurons. The researchers reported the new findings in a paper published in PLOS Genetics.

People with Alzheimer’s disease carry a mutation in their phospholipase D3 Gene. Nearly 1% of people with Alzheimer’s have this mutation. This mutation is rare and the protein’s function is unknown. In the new study, the researchers team looked into the function of this gene and its link to the disease. They also found that phospholipase D3  is located in lysosomes inside neurons.

Lysosomes are highly acidic sacs of enzymes that act as a recycling system of the cell. phospholipase D3 produces a component of the membrane of these acidic organelles, and this function is lost in the mutant form. People with occur  near buildups of toxic proteins called β-amyloid plaques. People with high levels of PLD3 had fewer β-amyloid plaques and less cognitive decline, suggesting that normal PLD3 helps protect against the disease.

Together, these discoveries establish the PLD3 mutation places a person at higher risk of developing Alzheimer’s disease, and can district the role of lysosome. They propose that studies should focus on investigating whether boosting PLD3 can have a protective effect that reduces the effects of the disease. These findings yield new drug targets for Alzheimer’s disease therapies and improve our understanding of the role of the lysosome in this common and burdensome disease.

Matthew Schrag of Vanderbilt University Medical Center said that the discovery of PLD3 as a genetic risk factor for  points to the critically important role of the lysosome in dementia. He experimental therapies to these lysosomes could lead us to new approaches to treat this disease.