Recent studies found the variants in Alzheimer's disease (AD) risk gene PLD3 were associated with cognitive function, but its detailed mechanism before typical AD onset was unknown. Our current study examined the impact of PLD3 common variant rs11667768 on cerebrospinal fluid (CSF) total-tau and phosphorylated-tau levels and structural MRI from the ADNI database. We found rs11667768 was significantly associated with CSF total-tau levels and hippocampal volumes at baseline and six-year follow-up in the total non-demented elderly group and the mild cognitive impairment subgroup, indicating a potential role of PLD3 common variants in influencing cognitive function through changing CSF total-tau levels and hippocampal volumes.