eng Science and Education Publishing American Journal of Food and Nutrition 2374-1163 2025-07-22 13 4 126 137 10.12691/ajfn-13-4-2 AJFN20251342 article Gabriela N. Lopez 1 Anna Goc 1 Matthias Rath 1 Aleksandra Niedzwiecki author@drrath.com 1 Dr. Rath Research Institute, San Jose, USA Alzheimer¡¯s disease (AD) is the most prevalent cause of dementia worldwide more frequently manifested in postmenopausal women. It has been associated in part with genetic predisposition (Apo E polymorphism) and chronic inflammation. We tested the effects of combinations of genistein with daidzein (SERMs), inositol hexa-phosphate with choline (phospholipid precursors), and the mixture (the Mix) of these two compositions with select plant extracts, vitamins, and minerals on specific AD cellular markers. The tests were conducted on fibroblasts derived from an old female AD patient and human normal dermal fibroblasts (HNDF) cultured under normal and inflammatory conditions. Evaluations included gene and protein expression for APOE, Tau and proinflammatory genes CSF2 and PTGS2. The Mix significantly decreased APOE gene expression in the cells derived from AD donor under normal and IL1¦Â-induced inflammatory conditions. In the presence of IL1¦Â and TNF¦Á, Tau gene expression was significantly lower in both HNDF and AD fibroblasts compared to control. In the presence of TNF¦Á Tau protein was affected by SERMs, phospholipids precursors, and the Mix. Test combinations differently affected the basal and inflammation-induced CSF2 and PTGS2 genes expression in HNDF and AD fibroblast. The effects of these natural compositions were compared to 17¦Â estradiol and inflammatory signaling pathways¡¯ inhibitors (SAPKs) to identify nutrients affecting specific cellular targets. This study indicates that nutrient combinations containing SERMs and/or phospholipid precursors, might exert the protective role of estrogens in relation to AD. These results merit further investigations aimed at developing effective natural approaches to AD and other forms of dementia. https://pubs.sciepub.com/ajfn/13/4/2/ajfn-13-4-2.pdf Inflammation Tau APOE Alzheimer¡¯s disease natural compounds