Targeting Synaptic Dysfunction in Alzheimer’s Disease by Administering a Specific Nutrient Combination
Open accessAbstract
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.
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Research shows a positive correlation between increased physical activity, cognitive training, improved nutrition, and slowing cognitive and functional decline and intensity of BPSD.
“Indeed, research shows a positive correlation between increased physical activity, cognitive training, improved nutrition, and slowing cognitive and functional decline and intensity of BPSD.”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [171]
The 'Clinical Utility of the Specific Nutrient Combination in AD' section reports improved memory after a specific nutritional intervention in patients with mild Alzheimer’s disease. It does not establish that physical activity or cognitive training slows decline, or that these approaches reduce functional decline or the intensity of behavioral and psychological symptoms of dementia (BPSD). The reported result is an intervention effect, not the broad correlation claimed. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPreclinical studies showed that administration of specific combinations of phospholipid synthesis-promoting nutrients can enhance neurotransmission and cognitive function.
“Preclinical studies showed that administration of specific combinations of the phospholipid synthesis-promoting nutrients can enhance neurotransmission and cognitive function [159].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [159]
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LECITHIN CONSUMPTION RAISES SERUM-FREE-CHOLINE LEVELS
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Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Alzheimer's Disease: Treatment Strategies and Their Limitations.
Passeri, E., Elkhoury, K., Morsink, M., Broersen, K., Linder, M., Tamayol, A., Malaplate, C., Yen, F. T., & Arab-Tehrany, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213954 · Cited by 592 · see citing works
Nutrition for the ageing brain: Towards evidence for an optimal diet
Vauzour, D., Camprubi-Robles, M., Miquel-Kergoat, S., Andres-Lacueva, C., Bánáti, D., Barberger-Gateau, P., Bowman, G. L., Caberlotto, L., Clarke, R., Hogervorst, E., et al. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.010 · Cited by 241 · see citing works
Self-citationSoininen, H., Solomon, A., Visser, P. J., Hendrix, S. B., Blennow, K., Kivipelto, M., Hartmann, T., Hallikainen, I., Hallikainen, M., Helisalmi, S., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30332-0 · Cited by 241 · see citing works
The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies
Perez-Pardo, P., Kliest, T., Dodiya, H. B., Broersen, L. M., Garssen, J., Keshavarzian, A., & Kraneveld, A. D. (2017) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2017.05.042 · Cited by 203 · see citing works
Self-citationBuccellato, F. R., D’Anca, M., Fenoglio, C., Scarpini, E., & Galimberti, D. (2021) · Antioxidants · doi:10.3390/antiox10091353 · Cited by 179 · see citing works
Mediterranean diet, micronutrients and macronutrients, and MRI measures of cortical thickness
Staubo, S. C., Aakre, J. A., Vemuri, P., Syrjanen, J. A., Mielke, M. M., Geda, Y. E., Kremers, W. K., Machulda, M. M., Knopman, D. S., Petersen, R. C., et al. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.06.2359 · Cited by 147 · see citing works
Gut-brain and brain-gut axis in Parkinson’s disease models: effects of a uridine and fish oil diet
Perez-Pardo, P., Dodiya, H. B., Broersen, L. M., Douna, H., van Wijk, N., Lopes da Silva, S., Garssen, J., Keshavarzian, A., & Kraneveld, A. D. (2018) · Nutritional Neuroscience · doi:10.1080/1028415x.2017.1294555 · Cited by 111 · see citing works
Self-citationShah, R. C., Kamphuis, P. J., Leurgans, S., Swinkels, S. H., Sadowsky, C. H., Bongers, A., Rappaport, S. A., Quinn, J. F., Wieggers, R. L., Scheltens, P., et al. (2013) · Alzheimer's Research & Therapy · doi:10.1186/alzrt224 · Cited by 112 · see citing works
Gu, X., Zhou, J., Zhou, Y., Wang, H., Si, N., Ren, W., Zhao, W., Fan, X., Gao, W., Wei, X., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00779-7 · Cited by 81 · see citing works
Perez-Pardo, P., de Jong, E. M., Broersen, L. M., van Wijk, N., Attali, A., Garssen, J., & Kraneveld, A. D. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00057 · Cited by 74 · see citing works
Self-citationOlde Rikkert, M. G. M., Verhey, F. R., Blesa, R., von Arnim, C. A. F., Bongers, A., Harrison, J., Sijben, J., Scarpini, E., Vandewoude, M. F. J., Vellas, B., et al. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-141305 · Cited by 61 · see citing works
Self-citationA Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice
Wiesmann, M., Zerbi, V., Jansen, D., Haast, R., Lütjohann, D., Broersen, L. M., Heerschap, A., & Kiliaan, A. J. (2016) · Neural Plasticity · doi:10.1155/2016/6846721 · Cited by 60 · see citing works
Self-citation
- Authors
- van Wijk, N., Broersen, L. M., de Wilde, M. C., Hageman, R. J. J., Groenendijk, M., Sijben, J. W. C., & Kamphuis, P. J. G. H.
- Affiliations
- Nutricia Advanced Medical Nutrition, Nutricia Research, Utrecht, The Netherlands
- Nutricia Research (Netherlands) (NL)
- Utrecht University (NL)
- ORCID
- Broersen, Laus M.
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2013-11-25
- Volume
- 38
- Issue
- 3
- Pages
- 459-479
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1504296704
- Cited by
- 128
- References
- 169
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 9 · 2023: 12 · 2022: 9 · 2021: 10 · 2020: 9 · 2019: 13 · 2018: 9 · 2017: 17 · 2016: 15 · 2015: 11 · 2014: 5 · 2013: 2
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- Alzheimer's disease, synaptic dysfunction
- MeSH terms
- Alzheimer Disease, Animals, Brain, Humans, Nutritional Status, Synapses, Dietary Supplements
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