PLD3 in non-familial Alzheimer's disease

Interest in the role of rare genetic variants in the aetiology of complex diseases such as Alzheimer's disease is increasing1,2. Recently, Cruchaga et al.3 provided evidence supporting the role of rare variants in the phospholipase D3 (PLD3) gene in both familial late-onset Alzheimer's disease (age at onset >65 years) and in non-familial Alzheimer's disease. In a follow-up study of 3,568 non-familial Alzheimer's disease cases and 3,867 controls of German or Spanish descent, we failed to replicate the latter finding. Our results therefore cast doubt on the aetiological relevance of rare coding PLD3 variants in non-familial Alzheimer's disease.