Thus, in this study, we find that chronic PLD1 inhibition (1 mg/kg VU01 once every 2 days i.p. for 30 days) at later stages of AD-like neuropathology, that has a greater dependence on tau, (with additional effects on neuroinflammation as well as astroglial mechanisms impinging on APOE-related dyslipidemia that need to be explored further) was sufficient to reduce PLD1 expression and association with amyloidogenic proteins, preserve dendritic spine morphology, improve hippocampal synaptic function and rescue hippocampal and amygdala-associative memory deficits. The gene discussed is PLD1; the disease is Alzheimer disease.