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- Title
Supplementation of Seaweed Extracts to the Diet Reduces Symptoms of Alzheimer's Disease in the APPswePS1ΔE9 Mouse Model.
- Authors
Martens, Nikita; Zhan, Na; Yam, Sammie C.; Leijten, Frank P. J.; Palumbo, Marcella; Caspers, Martien; Tiane, Assia; Friedrichs, Silvia; Li, Yanlin; van Vark-van der Zee, Leonie; Voortman, Gardi; Zimetti, Francesca; Jaarsma, Dick; Verschuren, Lars; Jonker, Johan W.; Kuipers, Folkert; Lütjohann, Dieter; Vanmierlo, Tim; Mulder, Monique T.
- Abstract
We previously demonstrated that diet supplementation with seaweed Sargassum fusiforme (S. fusiforme) prevented AD-related pathology in a mouse model of Alzheimer's Disease (AD). Here, we tested a lipid extract of seaweed Himanthalia elongata (H. elongata) and a supercritical fluid (SCF) extract of S. fusiforme that is free of excess inorganic arsenic. Diet supplementation with H. elongata extract prevented cognitive deterioration in APPswePS1ΔE9 mice. Similar trends were observed for the S. fusiforme SCF extract. The cerebral amyloid-β plaque load remained unaffected. However, IHC analysis revealed that both extracts lowered glial markers in the brains of APPswePS1ΔE9 mice. While cerebellar cholesterol concentrations remained unaffected, both extracts increased desmosterol, an endogenous LXR agonist with anti-inflammatory properties. Both extracts increased cholesterol efflux, and particularly, H. elongata extract decreased the production of pro-inflammatory cytokines in LPS-stimulated THP-1-derived macrophages. Additionally, our findings suggest a reduction of AD-associated phosphorylated tau and promotion of early oligodendrocyte differentiation by H. elongata. RNA sequencing on the hippocampus of one-week-treated APPswePS1ΔE9 mice revealed effects of H. elongata on, amongst others, acetylcholine and synaptogenesis signaling pathways. In conclusion, extracts of H. elongata and S. fusiforme show potential to reduce AD-related pathology in APPswePS1ΔE9 mice. Increasing desmosterol concentrations may contribute to these effects by dampening neuroinflammation.
- Subjects
ALZHEIMER'S disease prevention; ALZHEIMER'S disease; MACROPHAGES; PHOSPHORYLATION; RESEARCH funding; LIPIDS; NEUROGLIA; BRAIN; TREATMENT effectiveness; SYMPTOM burden; NEUROINFLAMMATION; CELLULAR signal transduction; PLANT extracts; MICE; IMMUNOHISTOCHEMISTRY; RNA probes; PHYTOSTEROLS; MARINE algae; ANIMAL experimentation; CLINICAL deterioration; COGNITION disorders; CHOLESTEROL; CYTOKINES; CELL differentiation; HIPPOCAMPUS (Brain); DIETARY supplements; BIOMARKERS; SEQUENCE analysis; ACETYLCHOLINE; SYMPTOMS
- Publication
Nutrients, 2024, Vol 16, Issue 11, p1614
- ISSN
2072-6643
- Publication type
Article
- DOI
10.3390/nu16111614