24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease

• Main Authors: Nikita Martens, Melissa Schepers, Na Zhan, Frank Leijten, Gardi Voortman, Assia Tiane, Ben Rombaut, Janne Poisquet, Nienke van de Sande, Anja Kerksiek, Folkert Kuipers, Johan W. Jonker, Hongbing Liu, Dieter Lütjohann, Tim Vanmierlo, Monique T. Mulder
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Marine Drugs
• Subjects: Alzheimer’s disease; seaweed; <i>Sargassum fusiforme</i>; phytosterols; cholesterol metabolism
• Online Access: https://www.mdpi.com/1660-3397/19/4/190

We recently found that dietary supplementation with the seaweed <i>Sargassum fusiforme</i>, containing the preferential LXRβ-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-β (Aβ) deposition in an Alzheimer’s disease (AD) mouse model without inducing hepatic steatosis. Here, we examined the effects of 24(S)-saringosterol as a food additive on cognition and neuropathology in AD mice. Six-month-old male APPswePS1ΔE9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1ΔE9 <i>n</i> = 20; C57BL/6J <i>n</i> = 19) or vehicle (APPswePS1ΔE9 <i>n</i> = 17; C57BL/6J <i>n</i> = 19) for 10 weeks. Cognition was assessed using object recognition and object location tasks. Sterols were analyzed by gas chromatography/mass spectrometry, Aβ and inflammatory markers by immunohistochemistry, and gene expression by quantitative real-time PCR. Hepatic lipids were quantified after Oil-Red-O staining. Administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice without affecting the Aβ plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1ΔE9 mice (<i>p</i> < 0.001). Furthermore, 24(S)-saringosterol did not affect the expression of lipid metabolism-related LXR-response genes in the hippocampus nor the hepatic neutral lipid content. Thus, administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice independent of effects on Aβ load and without adverse effects on liver fat content. The anti-inflammatory effects of 24(S)-saringosterol may contribute to the prevention of cognitive decline.