Reduced triacylglycerols and lipid droplets are associated with resilience to Alzheimer's disease

van der Vliet Daan, de Vries Luuk E., Di Xinyu, Wever Dennis, de Jong Brechtje, van der Meij Marc T. C., van der Peet Marielle, Harms Amy C., Hankemeier Thomas, Swaab Dick F., Huitinga Inge, Verhaagen Joost, van der Stelt Mario

doi:doi:10.1002/alz.71083

Persistent URL of this record https://hdl.handle.net/1887/4303524

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Faculty of Science: Other

van der Vliet Daan, de Vries Luuk E., Di Xinyu, Wever Dennis, de Jong Brechtje, van der Meij Marc T. C., van der Peet Marielle, Harms Amy C., Hankemeier Thomas, Swaab Dick F., Huitinga Inge, Verhaagen Joost, van der Stelt Mario (2026)

Reduced triacylglycerols and lipid droplets are associated with resilience to Alzheimer's disease

Article / Letter to editor

INTRODUCTION: Although it has become clear that alterations in lipid metabolism
are associated with Alzheimer’s disease (AD), it is unclear how they contribute to both
cognitive decline and the pathophysiology of AD.
METHODS: Lipidomics and activity-based protein profiling (ABPP) were performed
in the frontal cortex of control, AD and resilient donors, that is, individuals with AD
pathology without cognitive decline.
RESULTS: The most pronounced alterations in lipids were in ω6-derived oxylipins,
which were particularly increased in AD. Triacylglycerols (TAGs) and lipid droplets
(LDs) were more abundant in the AD donors compared to the resilient donors. Multi-
omics factor analysis (MOFA) showed that increased ω6-derived oxylipins and the loss
of inhibitory neurons were associated with amyloid beta (Aβ) plaque load.
DISCUSSION: Our multi-omics data show a molecular response associated with Aβ
load shared among AD and resilient donors, but...Show moreINTRODUCTION: Although it has become clear that alterations in lipid metabolism
are associated with Alzheimer’s disease (AD), it is unclear how they contribute to both
cognitive decline and the pathophysiology of AD.
METHODS: Lipidomics and activity-based protein profiling (ABPP) were performed
in the frontal cortex of control, AD and resilient donors, that is, individuals with AD
pathology without cognitive decline.
RESULTS: The most pronounced alterations in lipids were in ω6-derived oxylipins,
which were particularly increased in AD. Triacylglycerols (TAGs) and lipid droplets
(LDs) were more abundant in the AD donors compared to the resilient donors. Multi-
omics factor analysis (MOFA) showed that increased ω6-derived oxylipins and the loss
of inhibitory neurons were associated with amyloid beta (Aβ) plaque load.
DISCUSSION: Our multi-omics data show a molecular response associated with Aβ
load shared among AD and resilient donors, but reduced LDs in resilient donors
compared to AD.
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