Omega‐3 polyunsaturated fatty acids promote amyloid‐β clearance from the brain through mediating the function of the glymphatic system

Ren, Huixia; Luo, Chuanming; Feng, Yanqing; Yao, Xiaoli; Shi, Zhe; Liang, Fengyin; Kang, Jing; Wan, Jian‐Bo; Pei, Zhong; Su, Huanxing

doi:10.1096/fj.201600896

Cited by 93 publications

(76 citation statements)

References 52 publications

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“…On the other hand, there have been many reports that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) relate closely to brain functions (Grimm et al, 2016, Hopperton et al, 2016, Ren et al, 2017). Scallop-derived Pls used in the present study presumably contained relatively large amounts of DHA and EPA (Kraffe et al, 2004, Hanuš et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Blood Plasmalogen Changes by Oral Administration of Plasmalogen in Patients with Mild Alzheimer's Disease and Mild Cognitive Impairment: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial

Yamada²,

et al. 2017

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BackgroundPlasmalogens (Pls) reportedly decreased in postmortem brain and in the blood of patients with Alzheimer's disease (AD). Recently we showed that intraperitoneal administration of Pls improved cognitive function in experimental animals. In the present trial, we tested the efficacy of oral administration of scallop-derived purified Pls with respect to cognitive function and blood Pls changes in patients with mild AD and mild cognitive impairment (MCI).MethodsThe study was a multicenter, randomized, double-blind, placebo-controlled trial of 24 weeks. Participants were 328 patients aged 60 to 85 years who had 20 to 27 points in Mini Mental State Examination-Japanese (MMSE-J) score and five or less points in Geriatric Depression Scale-Short Version-Japanese (GDS-S-J). They were randomized to receive either 1 mg/day of Pls purified from scallop or placebo. The patients and study physicians were masked to the assignment. The primary outcome was MMSE-J. The secondary outcomes included Wechsler Memory Scale-Revised (WMS-R), GDS-S-J and concentration of phosphatidyl ethanolamine plasmalogens (PlsPE) in erythrocyte membrane and plasma. This trial is registered with the University Hospital Medical Information Network, number UMIN000014945.FindingsOf 328 patients enrolled, 276 patients completed the trial (140 in the treatment group and 136 in the placebo group). In an intention-to-treat analysis including both mild AD (20 ≤ MMSE-J ≤ 23) and MCI (24 ≤ MMSE-J ≤ 27), no significant difference was shown between the treatment and placebo groups in the primary and secondary outcomes, with no severe adverse events in either group. In mild AD patients, WMS-R improved significantly in the treatment group, and the between group difference was nearly significant (P = 0.067). In a subgroup analysis of mild AD patients, WMS-R significantly improved among females and those aged below 77 years in the treatment group, and the between-group differences were statistically significant in females (P = 0.017) and in those aged below 77 years (P = 0.029). Patients with mild AD showed a significantly greater decrease in plasma PlsPE in the placebo group than in the treatment group.InterpretationOral administration of scallop-derived purified Pls may improve cognitive functions of mild AD.Funding.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Blood Plasmalogen Changes by Oral Administration of Plasmalogen in Patients with Mild Alzheimer's Disease and Mild Cognitive Impairment: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial

Yamada²,

et al. 2017

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“…The MD has been established as of benefit to AD sufferers (17,19,24,181) preventative measure have become more evident (183,184); however, findings on its effect on S100β levels are still inconclusive.…”

Section: Mediterranean Dietmentioning

confidence: 99%

Evaluation of dietary and lifestyle changes as modifiers of S100β levels in Alzheimer’s disease

D’Cunha

McKune

Panagiotakos

et al. 2017

Nutritional Neuroscience

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There is a significant body of research undertaken in order to elucidate the mechanisms underlying the pathology of Alzheimer's disease (AD), as well as to discover early detection biomarkers and potential therapeutic strategies. One such proposed biomarker is the calcium binding protein S100β, which, depending on its local concentration, is known to exhibit both neurotrophic and neuroinflammatory properties in the central nervous system. At present, relatively little is known regarding the effect of chronic S100β disruption in AD. Dietary intake has been identified as a modifiable risk factor for AD. Preliminary in vitro and animal studies have demonstrated an association between S100β expression and dietary intake which links to AD pathophysiology. This review describes the association of S100β to fatty acids, ketone bodies, insulin, and botanicals as well as the potential impact of physical activity as a lifestyle factor. We also discuss the prospective implications of these findings, including support of the use of a Mediterranean dietary pattern and/or the ketogenic diet as an approach to modify AD risk.

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“…Aquaporin 4 (AQP4) is a major component of the lymphatic–glymphatic system, and is normally expressed in the end-feet of the astrocytes that facilitate paravascular cerebrospinal fluid (CSF)–interstitial fluid (ISF) exchange (Iliff et al, 2012). However, in aged-brain-related astrogliosis, AQP4 relocalizes from the feet to the somata of astrocytes, thus preventing paravascular CSF–ISF exchange (Ren et al, 2017). …”

Section: Introductionmentioning

confidence: 99%

Voluntary Exercise Promotes Glymphatic Clearance of Amyloid Beta and Reduces the Activation of Astrocytes and Microglia in Aged Mice

Liu

Zhang

et al. 2017

Front. Mol. Neurosci.

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253

192

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Age is characterized by chronic inflammation, leading to synaptic dysfunction and dementia because the clearance of protein waste is reduced. The clearance of proteins depends partly on the permeation of the blood–brain barrier (BBB) or on the exchange of water and soluble contents between the cerebrospinal fluid (CSF) and the interstitial fluid (ISF). A wealth of evidence indicates that physical exercise improves memory and cognition in neurodegenerative diseases during aging, such as Alzheimer’s disease (AD), but the influence of physical training on glymphatic clearance, BBB permeability and neuroinflammation remains unclear. In this study, glymphatic clearance and BBB permeability were evaluated in aged mice using in vivo two-photon imaging. The mice performed voluntary wheel running exercise and their water-maze cognition was assessed; the expression of the astrocytic water channel aquaporin 4 (AQP4), astrocyte and microglial activation, and the accumulation of amyloid beta (Aβ) were evaluated with immunofluorescence or an enzyme-linked immunosorbent assay (ELISA); synaptic function was investigated with Thy1–green fluorescent protein (GFP) transgenic mice and immunofluorescent staining. Voluntary wheel running significantly improved water-maze cognition in the aged mice, accelerated the efficiency of glymphatic clearance, but which did not affect BBB permeability. The numbers of activated astrocytes and microglia decreased, AQP4 expression increased, and the distribution of astrocytic AQP4 was rearranged. Aβ accumulation decreased, whereas dendrites, dendritic spines and postsynaptic density protein (PSD95) increased. Our study suggests that voluntary wheel running accelerated glymphatic clearance but not BBB permeation, improved astrocytic AQP4 expression and polarization, attenuated the accumulation of amyloid plaques and neuroinflammation, and ultimately protected mice against synaptic dysfunction and a decline in spatial cognition. These data suggest possible mechanisms for exercise-induced neuroprotection in the aging brain.

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Omega‐3 polyunsaturated fatty acids promote amyloid‐β clearance from the brain through mediating the function of the glymphatic system

Cited by 93 publications

References 52 publications

Efficacy and Blood Plasmalogen Changes by Oral Administration of Plasmalogen in Patients with Mild Alzheimer's Disease and Mild Cognitive Impairment: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial

Efficacy and Blood Plasmalogen Changes by Oral Administration of Plasmalogen in Patients with Mild Alzheimer's Disease and Mild Cognitive Impairment: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial

Evaluation of dietary and lifestyle changes as modifiers of S100β levels in Alzheimer’s disease

Voluntary Exercise Promotes Glymphatic Clearance of Amyloid Beta and Reduces the Activation of Astrocytes and Microglia in Aged Mice

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