Investigating the association of lipidome profiles with central Alzheimer's disease (AD) biomarkers, including amyloid/tau/neurodegeneration (A/T/N), can provide a holistic view between the lipidome and AD. We performed cross-sectional and longitudinal association analysis of serum lipidome profiles with AD biomarkers in the Alzheimer's Disease Neuroimaging Initiative cohort (N=1,395). We identified lipid species, classes, and network modules that were significantly associated with cross-sectional and longitudinal changes of A/T/N biomarkers for AD. Notably, we identified the lysoalkylphosphatidylcholine (LPC(O)) as associated with "A/N" biomarkers at baseline at lipid species, class, and module levels. Also, GM3 ganglioside showed significant association with baseline levels and longitudinal changes of the "N" biomarkers at species and class levels. Our study of circulating lipids and central AD biomarkers enabled identification of lipids that play potential roles in the cascade of AD pathogenesis. Our results suggest dysregulation of lipid metabolic pathways as precursors to AD development and progression.