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Review
. 2022 Feb 1;33(1):16-24.
doi: 10.1097/MOL.0000000000000801.

Lipids and brain inflammation in APOE4-associated dementia

Marlon V Duro  1 , Brandon Ebright  2 , Hussein N Yassine  3
Affiliations
Review

Lipids and brain inflammation in APOE4-associated dementia

Marlon V Duro et al. Curr Opin Lipidol. .

Abstract

Purpose of review: To highlight recent developments in studying mechanisms by which the apolipoprotein E4 (APOE4) allele affects the metabolism of brain lipids and predisposes the brain to inflammation and Alzheimer's disease (AD) dementia.

Recent findings: APOE4 activates Ca2+ dependent phospholipase A2 (cPLA2) leading to changes in arachidonic acid (AA), eicosapentaenoic acid and docosahexaenoic acid signaling cascades in the brain. Among these changes, the increased conversion of AA to eicosanoids associates with sustained and unresolved chronic brain inflammation. The effects of APOE4 on the brain differ by age, disease stage, nutritional status and can be uncovered by brain imaging studies of brain fatty acid uptake. Reducing cPLA2 expression in the dementia brain presents a viable strategy that awaits to be tested.

Summary: Fatty acid brain imaging techniques can clarify how changes to brain polyunsaturated fatty acid metabolism during the various phases of AD and guide the development of small molecules to mitigate brain inflammation.

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Conflict of interest statement

Conflicts of interest

There are no conflicts of interest.

Figures

Figure 1.
Figure 1.
An illustration of the Lands cycle and how increased cPLA2 activation can liberate free AA which can be converted to pro-inflammatory mediators. cPLA2 activation has multiple cell specific effects on the different brain cells and is accentuated by APOE4.
Figure 2.
Figure 2.
PET/MRI image of a mouse 30 min and 60 min after a tail vein bolus injection of 20-[18F]fluoro-AA (270.4 μCi dose). Arrows indicate areas where PUFA has accumulated in the brain after uptake over time
See this image and copyright information in PMC

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