Circulating lipid profiles are associated with cross-sectional and longitudinal changes of central biomarkers for Alzheimer’s disease

Abstract

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.

Signatures and Discriminative Abilities of Multi-Omics between States of Cognitive Decline

“…However, the available literature is still limited and presents heterogeneity [13][14][15]. Lysophosphatidylcholines and dehydrodesmosterol ester alterations are documented in AD pathology and are associated with its progression [16]. Regarding CSF proteomics, apolipoprotein E, neural pentraxin-2, and fatty-acid-binding protein have been implicated in neurodegeneration, which are markers of prognosis [7], synaptic function, amyloid deposition [17], and neuronal membrane disruption [18], respectively.…”