Immunotherapy of Mild Cognitive Impairment by ω-3 Supplementation: Why Are Amyloid-ß Antibodies and ω-3 Not Working in Clinical Trials?
J Alzheimers Dis
; 62(3): 1013-1022, 2018.
Article
em En
| MEDLINE
| ID: mdl-29103035
ABSTRACT
This article reviews the basic tenets of a clinical approach to effective immunotherapy of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI). Although one randomized controlled study in early MCI patients by fish-derived omega-3 fatty acids (ω-3) showed slowing of disease progression, large clinical trials with different products have failed to show cognitive effects. Macrophages of healthy subjects phagocytize and degrade amyloid-ß1 - 42 (Aß) in the brain tissues, whereas macrophages of patients with AD and MCI are functionally defective. ω-3 and ω-3-derived specialized proresolving mediators (SPMs), such as resolvin D1, have powerful biochemical and immunological effects, which may repair the functions of MCI patients' macrophages in the brain's clearance of Aß. Unfortunately, ω-3 products on the market have a variable quality. Nutritional supplementation with a combination drink called Smartfish with an emulsion of ω-3 and other fatty acids, antioxidants, 1,25-dihydroxy vitamin D3, and resveratrol improved the innate immune system of MCI patients by modulation of macrophage type to the pro-phagocytic M1-M2 type with an effective unfolded protein response against endoplasmic reticulum stress. Some MCI patients maintained their initial cognitive status for three years on Smartfish supplementation. Future randomized clinical trials should investigate the immune effects of ω-3, 1,25-dihydroxy vitamin D3, and SPMs on macrophage type, function, and biochemistry in parallel with cognitive effects.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Graxos Ômega-3
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Suplementos Nutricionais
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Disfunção Cognitiva
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Imunoterapia
Tipo de estudo:
Clinical_trials
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Alzheimers Dis
Ano de publicação:
2018
Tipo de documento:
Article