P4–265: Mechanism of action of the specific nutrient combination Fortasyn® Connect, which is designed to enhance synapse formation and function in Alzheimer's disease

Synapse loss has been recognized to be the strongest structural correlate with memory impairment in Alzheimer's disease (AD) and is apparent already early in the disease process. Synapses and neurites consist of neuronal membranes largely composed of phospholipids. Synapse loss and synaptic dysfunction in AD are linked to neuronal membrane loss and altered membrane composition. The formation of new synapses requires the synthesis of new neuronal membranes. Dietary interventions that increase the availability of nutritional compounds, which support neuronal membrane formation and function, potentially counter synaptic loss in AD. In vitro and in vivo studies have demonstrated that supplementation with the phospholipid precursors DHA (docosahexaenoic acid) and/or EPA (eicosapentaenoic acid), UMP (uridine monophosphate), and choline not only increases the synthesis of membrane phospholipids, but also increases neurite outgrowth, levels of specific pre- or post-synaptic proteins, and the number of dendritic spines, all prerequisites for new synapse formation. Other nutrients, i.e. B-vitamins, vitamin C and E, selenium, and dietary phospholipids, were shown to act as cofactors by increasing the availability of membrane precursors or by directly affecting the neuronal membrane or membrane synthesis. Supplementation of combinations of these membrane precursors and cofactors was also shown to modulate membrane-related processes, such as neurotransmission, Aβ-related pathology, and ultimately cognitive performance. Based on these insights, the specific nutrient combination Fortasyn ® Connect (UMP, DHA, EPA, choline, phospholipids, folate, vitamins B 6, B 12, C and E, and selenium) was designed to enhance synapse formation and function in AD patients. Recent preclinical experiments with Fortasyn Connect confirm the hypothesis that nutrients in Fortasyn Connect act in concert to enhance synapse formation and functioning, and to ameliorate cognitive dysfunction. The medical food Souvenaid®, containing Fortasyn Connect, is a nutritional intervention for the management of early AD. A clinical study program is investigating the efficacy of Souvenaid. The clinical studies to date provide evidence that Souvenaid has a beneficial effect on memory function in mild AD and support the hypothesis that enhancing synaptic function in the mild stage of AD may be related to improved memory performance.