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Stigmasterol may help against Alzheimers

A complex study using mice, reported in the Journal of Neuroscience, evaluated whether the dietary intake of plant sterols might be beneficial for the prevention of Alzheimers Disease (AD). This was done by analysing the effect of plant sterols and cholesterol on processing of amyloid precursor protein (APP). This is of interest since Amyloid-β (Aβ), generated by proteolytic processing of APP by β- and γ-secretase, is a major constituent of senile plaques in AD.
The research team found that stigmasterol was the only plant sterol that significantly decreased Aβ levels. Compared with stigmasterol, β-sitosterol and cholesterol significantly increased Aβ levels, whereas campesterol and brassicasterol showed minor or no effect.
The authors note that stigmasterol is structurally the most distinctive from cholesterol, having an additional double-bond at C22–C23 and an ethylgroup at C24. The analysis of the molecular mechanisms revealed that stigmasterol directly inhibited b-secretase activity and further reduced β-secretase cleavage of APP.
Other effects were also noted, and the research team notes that stigmasterol-induced effects were all between 10% and 30% and less pronounced compared with synthetic secretase inhibitors. However, these obviously minor effects on different cellular processes, including direct modulation of enzymes, gene expression, and subcellular transport processes, reduced Aβ generation by 38%.
Overall the authors conclude that a diet enriched in plant sterols mainly containing stigmasterol might be beneficial for AD. Their data show that plant sterols are biologically active food compounds interfering with important functional processes in the brain. However, they also warn that phytosterols might interfere with other brain functions such as cell signaling, neurotransmission, and membrane protein transport and these should be addressed by further studies.

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