Gabriela N. Lopez¹, Anna Goc¹, Matthias Rath¹, Aleksandra Niedzwiecki^1,

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 IL1β-induced inflammatory conditions. In the presence of IL1β and TNFα, Tau gene expression was significantly lower in both HNDF and AD fibroblasts compared to control. In the presence of TNFα 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 17β 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.

Inflammation, Tau, APOE, Alzheimer’s disease, natural compounds