Reduced triacylglycerols and lipid droplets are associated with resilience to Alzheimer’s disease
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Introduction
While it has become clear that alterations in lipid metabolism are associated with AD, it is unclear how they contribute to both cognitive decline and the pathophysiology of AD.
Methods
We performed lipidomics and activity-based protein profiling in the frontal cortex of control, AD and resilient donors, i.e. individuals with AD pathology without cognitive decline. Subsequently we integrated these data using multi-omics factor analysis and correlated the multi-omics profiles to disease and clinical parameters.
Results
The most pronounced alterations in lipids were in the ω6-derived oxylipins, which were particularly increased in the AD patients. Both triacylglycerols (TAGs) and lipid droplets were more abundant in the AD donors compared to the resilient donors. Enzyme activities showed a similar direction in the AD and resilient donors, including decreased activity of ABHD6. Multi-omics factor analysis showed that increased oxylipins, loss of inhibitory cells, synaptic genes and genes related to the inflammatory response were associated with Aβ plaque load in both AD and resilient donors.
Conclusion
Our multi-omics data show a response associated with Aβ load shared among AD and resilient donors and, for the first time, reduced lipid droplets in resilient donors.
