Targeting Synaptic Dysfunction in Alzheimer's Disease by Administering a Specific Nutrient Combination

Abstract

Synapse loss and synaptic dysfunction are pathological processes already involved in the early stages of Alzheimer's disease (AD). Synapses consist principally of neuronal membranes, and the neuronal and synaptic losses observed in AD have been linked to the degeneration and altered composition and structure of these membranes. Consequently, synapse loss and membrane-related pathology provide viable targets for intervention in AD. The specific nutrient combination Fortasyn Connect (FC) is designed to ameliorate synapse loss and synaptic dysfunction in AD by addressing distinct nutritional needs believed to be present in these patients. This nutrient combination comprises uridine, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium, and is present in Souvenaid, a medical food intended for use in early AD. It has been hypothesized that FC counteracts synaptic loss and reduces membrane-related pathology in AD by providing nutritional precursors and cofactors that act together to support neuronal membrane formation and function. Preclinical studies formed the basis of this hypothesis which is being validated in a broad clinical study program investigating the potential of this nutrient combination in AD. Memory dysfunction is one key early manifestation in AD and is associated with synapse loss. The clinical studies to date show that the FC-containing medical food improves memory function and preserves functional brain network organization in mild AD compared with controls, supporting the hypothesis that this intervention counteracts synaptic dysfunction. This review provides a comprehensive overview of basic scientific studies that led to the creation of FC and of its effects in various preclinical models.

Souvenaid Reduces Behavioral Deficits and Improves Social Cognition Skills in Frontotemporal Dementia: A Proof-of-Concept Study

“…Previous studies have shown the potential of these compounds to increase both neurite outgrowth and the number of dendritic spines as well as the levels of pre- or post-synaptic proteins, thus suggesting the ability of Souvenaid™ to improve synaptic structural integrity [2,3,4]. Moreover, Souvenaid™ has been shown to have a positive impact on the cognitive function in patients with mild Alzheimer's disease (AD) [5], pointing to the clinical efficacy of this therapeutic approach.…”

“…Despite the possible clinical usefulness of targeting synaptic dysfunction, the currently available pharmacological options to reach this aim in the clinical setting are limited. Restoring synaptic function, however, represents one of the main targets of nutraceuticals (medical foods), that is, dietary supplements designed to meet the nutritional requirements specifically identified for a clinical purpose [2]. …”

“…Souvenaid™ (Nutricia N.V., Zoetermeer, the Netherlands) is a medical food composed of uridine-mono-phosphate, docosahexaenoic acid (DHA), choline, eicosapentaenoic acid (EPA), selenium, folic acid, phospholipids and B vitamins, which are all the precursors and cofactors required for the formation of neuronal membranes [2]. Previous studies have shown the potential of these compounds to increase both neurite outgrowth and the number of dendritic spines as well as the levels of pre- or post-synaptic proteins, thus suggesting the ability of Souvenaid™ to improve synaptic structural integrity [2,3,4].…”

Alternative Approaches in the Prevention of Alzheimer’s Disease

“…Recently, other non-invasive therapies such as music therapy (Balbag, Pedersen, & Gatz, 2015) or multi-nutrient intervention in form of medical foods (Van Wijk et al, 2014;Weiqian, van Wijk, Cansev, Sibjen, & Kamphuis, 2013) can be good protective factors against the development of AD. Table 1 below demonstrates the key benefits and limitations of these therapies in the prevention of AD.…”

Review on Therapeutic Effects Mediated by Omega-3 Fatty Acids in Alzheimer’s Disease

“…Souvenaid (Nutricia N.V., Zoetermeer, the Netherlands), containing the specific nutrient combination Fortasyn Connect, has been designed to enhance synapse formation and function in AD compared to control product without the specific nutrient [104,105]. Souvenaid is a product intended as a medical food for oral consumption under medical supervision with the purpose of addressing disease-specific nutrient requirements.…”