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Scientists working at the Dr. Rath Research Institute have recently been exploring the effects of various natural compounds on Alzheimer’s disease (AD). Their approach examines the impact of these compounds on skin fibroblast cells derived from both young and old female AD patients, and compares them to normal human dermal fibroblast cells. The study, published in the American Journal of Food and Nutrition, aims to understand how natural compounds influence significant markers in the pathology of AD: the expression of the Apolipoprotein E (ApoE) gene, the production of the ApoE protein coded by this gene, and levels of the Tau protein.
Since inflammation plays an important role in the development of AD and other neurodegenerative processes, the experiments were conducted under both normal and pro-inflammatory conditions that might alter the response of cells to the compounds. Several natural substances were tested as possible modulators of AD markers, including vitamins, soybean isoflavones (genistein and daidzein), phospholipid synthesis precursors such as inositol and choline, and phosphatidylserine, a major membrane phospholipid.
So how does ApoE relate to AD? While we frequently hear about amyloid plaques accumulating in the brains of patients affected by AD, or the presence of intracellular structures composed of aggregated Tau protein, ApoE is not so often referred to. In fact, this protein functions as a lipid transporter responsible for delivering cholesterol and phospholipids to various cells, including neurons. Problems with the ability of brain cells to process lipids have been linked not just to the development of AD, but also various other neurological pathologies as well. The ApoE gene, in particular its ApoE4 form, has been identified in more than half of AD cases.
As ApoE contributes to disease progression by influencing both Tau and amyloid plaque pathology, achieving a better understanding of the effects of natural compounds on ApoE and Tau might provide us with critical information towards developing therapeutic strategies for AD and other neurodegenerative diseases. The risk of AD is higher in women than in men and increases with age. The Dr. Rath Research Institute’s scientists therefore studied the effects of nutrients on cells derived from young and old female patients and compared them with normal cells.
The study revealed several differences regarding how cells derived from young and old AD patients responded to nutrients. In young AD cells, the plant estrogenic compound daidzein, and inositol, a sugar-like compound present in cellular membranes, could lower the levels of the APOE protein. Conversely, phosphatidylserine and another estrogenic compound, genistein, increased it. Interestingly, in old AD cells, with the exception of vitamin C, all of the tested natural compounds increased APOE protein levels. In normal cells, almost all of the compounds significantly reduced its levels.
When looking at the Tau protein, which plays a crucial role in AD, the study found that in young AD cells, daidzein and phosphatidylserine almost completely inhibited its levels. Inositol and genistein were also effective in achieving this. Both inositol and choline were very effective in decreasing Tau in cells derived from old AD patients. In the presence of these compounds, Tau levels were almost undetectable. However, they had an opposite effect on normal cells, with daidzein, phosphatidylserine, inositol, and choline increasing Tau levels, while vitamin C had no effect.
It is important to know how nutrients can affect ApoE and Tau under the inflammatory conditions commonly seen in AD. Such conditions were imitated in these experiments by exposing cells to the pro-inflammatory cytokine IL1β. The results showed that inflammation slightly increased APOE protein levels in young AD cells. This was reduced by daidzein, while other compounds had no significant impact. However, inflammation affected Tau protein levels differently, increasing it in cells from both young and old AD patients but not in normal cells. Under inflammation, all compounds apart from phosphatidylserine decreased Tau protein levels in young AD cells, while in old AD cells genistein, daidzein, and phosphatidylserine had similar inhibitory effects to those seen in cells serving as the controls.
This Dr. Rath Research Institute study shows for the first time the complex interactions between natural compounds and important biomarkers of AD, revealing that these are highly dependent on cell type, age, and environmental conditions. As a result of their significant effects in reducing the ApoE and Tau protein levels that are important in AD cells, the study identified that the selective estrogen receptor modulator daidzein, and a structural component of lipids, inositol, are particularly promising for further research. The study adds to the growing body of evidence showing that natural compounds could play a role in the treatment of AD, potentially offering new avenues for therapeutic development in other brain pathologies as well.