Although the cause of
Alzheimer's disease (AD) is unknown, glial-induced
neuroinflammation is an early symptom. Familial AD is caused by increases in
amyloid-beta (Aβ)
peptide, particularly soluble oligomeric (oAβ), considered a proximal
neurotoxin and neuroinflammatory stimuli.
APOE4, a naturally occurring genotype of
APOE, is the greatest genetic risk factor for AD; increasing risk up to 12-fold compared to
APOE3 and
APOE2. oAβ-induced
neuroinflammation is greater with
APOE4 compared to
APOE3 and
APOE2. As sinapates and
flavonoids have anti-inflammatory properties, a protocol was developed for optimizing
polyphenol production in seedlings of Arabidopsis thaliana (A. thaliana). Three mutants (cop1,
prn1, xpf3) were identified, and the extracts treated with liver microsomes to mimic physiological metabolism, with HPLC and MS performed on the resulting metabolites for peak identification. These extracts were used to treat primary glial cells isolated from human
APOE-targeted-replacement (
APOE-TR) and
APOE-knock-out (KO) mice, with
neuroinflammation induced by
lipopolysaccharide (LPS) or oAβ. The dose-response data for TNFα secretion demonstrate the followed the order:
APOE-KO > APOE4 > APOE3 > APOE2, with xpf3 the most effective anti-neuroinflammatory across
APOE genotypes. Thus, the plant-based approach described herein may be particularly valuable in treating the APOE4-induced neuroinflammatory component of AD risk.