Extra-virgin olive oil attenuates amyloid-β and tau pathologies in the brains of TgSwDI mice

Qosa, Hisham; Mohamed, Loqman A.; Batarseh, Yazan S.; Alqahtani, Saeed; Ibrahim, Baher A.; LeVine, Harry; Keller, Jeffrey N.; Kaddoumi, Amal

doi:10.1016/j.jnutbio.2015.07.022

Cited by 86 publications

(76 citation statements)

References 63 publications

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“…This was associated with a significant decrease in the A β immunoreactivity in the cortex and hippocampus brain regions of the same mice suggesting that A β deposition was significantly affected in the EVOO treated group. When we assessed the proteolytic enzymes and pathways involved in the APP metabolism differently from another report we observed that compared with controls, the treated mice had an increase in α ‐secretase and β ‐secretase and their products, s‐APP α and the sAPP β 11. While that study does not provide data on these two proteases, we think that the discrepancy in the result for the sAPP β could be secondary to the different mouse model implemented by the authors 11.…”

Section: Discussionmentioning

confidence: 82%

“…When we assessed the proteolytic enzymes and pathways involved in the APP metabolism differently from another report we observed that compared with controls, the treated mice had an increase in α ‐secretase and β ‐secretase and their products, s‐APP α and the sAPP β 11. While that study does not provide data on these two proteases, we think that the discrepancy in the result for the sAPP β could be secondary to the different mouse model implemented by the authors 11. Moreover, by contrast with other reports, we were not able to show any effect of the EVOO on some of the major protein systems in place to control A β clearance and degradation 29.…”

Section: Discussionmentioning

confidence: 82%

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Extra-virgin olive oil ameliorates cognition and neuropathology of the 3xTg mice: role of autophagy

Lauretti

Iuliano

Praticò

2017

Ann Clin Transl Neurol

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ObjectiveConsumption of extra virgin olive oil (EVOO), a major component of the Mediterranean diet, has been associated with reduced incidence of Alzheimer's disease (AD). However, the mechanisms involved in this protective action remain to be fully elucidated.MethodsHerein, we investigated the effect of daily consumption of EVOO on the AD‐like phenotype of a mouse mode of the disease with plaques and tangles.ResultsTriple transgenic mice (3xTg) received either regular chow or a chow diet supplemented with EVOO starting at 6 months of age for 6 months, then assessed for the effect of the diet on the AD‐like neuropathology and behavioral changes. Compared with controls, mice receiving the EVOO‐rich diet had an amelioration of their behavioral deficits, and a significant increase in the steady state levels of synaptophysin, a protein marker of synaptic integrity. In addition, they had a significant reduction in insoluble Aβ peptide levels and deposition, lower amount of phosphorylated tau protein at specific epitopes, which were secondary to an activation of cell autophagy.InterpretationTaken together, our findings support a beneficial effect of EVOO consumption on all major features of the AD phenotype (behavioral deficits, synaptic pathology, Aβ and tau neuropathology), and demonstrate that autophagy activation is the mechanism underlying these biological actions.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 82%

Extra-virgin olive oil ameliorates cognition and neuropathology of the 3xTg mice: role of autophagy

Lauretti

Iuliano

Praticò

2017

Ann Clin Transl Neurol

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“…Recently, several lines of evidence have demonstrated the health effects of extra virgin olive oil (EVOO) and have suggested that its consumption ameliorates age‐related memory decline and decrease the risk of AD onset (Farr et al, ; Feart, Samieri, Alles, & Barberger‐Gateau, ; Pitozzi et al, ). While most of the experimental studies have been focusing on the ability of EVOO to enhance Aβ clearance and reduce its deposition (Abuznait, Qosa, Busnena, El Sayed, & Kaddoumi, ; Qosa et al, ), only fewer research groups have been investigating the tau‐modifying ability of EVOO. On this regard, studies reported that some natural phenolic derivatives from olives, as well as oleocanthal, can prevent tau fibrillization in vitro (Daccache et al, ; Monti, Margarucci, Tosco, Riccio, & Casapullo, ).…”

Section: Introductionmentioning

confidence: 99%

Extra virgin olive oil improves synaptic activity, short‐term plasticity, memory, and neuropathology in a tauopathy model

et al. 2019

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In recent years, increasing evidence has accumulated supporting the health benefits of extra virgin olive oil (EVOO). Previous studies showed that EVOO supplementation improves Alzheimer's disease (AD)‐like amyloidotic phenotype of transgenic mice. However, while much attention has been focused on EVOO‐mediated modulation of Aβ processing, its direct influence on tau metabolism in vivo and synaptic function is still poorly characterized. In this study, we investigated the effect of chronic supplementation of EVOO on the phenotype of a relevant mouse model of tauopathy, human transgenic tau mice (hTau). Starting at 6 months of age, hTau mice were fed chow diet supplemented with EVOO or vehicle for additional 6 months, and then the effect on their phenotype was assessed. At the end of the treatment, compared with control mice receiving EVOO displayed improved memory and cognition which was associated with increased basal synaptic activity and short‐term plasticity. This effect was accompanied by an upregulation of complexin 1, a key presynaptic protein. Moreover, EVOO treatment resulted in a significant reduction of tau oligomers and phosphorylated tau at specific epitopes. Our findings demonstrate that EVOO directly improves synaptic activity, short‐term plasticity, and memory while decreasing tau neuropathology in the hTau mice. These results strengthen the healthy benefits of EVOO and further support the therapeutic potential of this natural product not only for AD but also for primary tauopathies.

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“…From this homogenate, 100 µl were centrifuged at 20,817 x g for 15 min at 4 °C to collect supernatant/lysate that contain soluble Aβ. To measure oligomeric and insoluble Aβ from total brain homogenate, a 2-step serial extraction procedure was used as described previously with modification 62 . In brief, the remained pellet following soluble Aβ extraction was mixed with 2% SDS in PBS containing protease arrest with homogenization, followed by sonication for 10 min and centrifugation at 20,817 x g for 60 min at 22 °C.…”

Section: Analysis Of Aβ Burden In Mice Brainsmentioning

confidence: 99%

“…All brains slices were methanol-fixed and blocked for 30 min with 10% normal donkey serum in PBS. For the detection of Aβ-plaques load, we followed a previously published protocol with slight modification 62 . Briefly, the sections were immuostained with rabbit polyclonal collagen IV antibody (1:200) to detect brain microvessels followed by donkey polyclonal Alexa Flour 647 antibody to rabbit IgG (1:200), which were then incubated in filtered 0.02% thioflavin-S (Thio-S) solution prepared in 70% ethanol for 30 min to detect Aβ deposits.…”

Section: Analysis Of Aβ Burden In Mice Brainsmentioning

confidence: 99%

Amylin and pramlintide modulate γ-secretase level and APP processing in lipid rafts

Mousa

Abdallah

Hwang

et al. 2020

Sci Rep

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A major characteristic of Alzheimer's disease (AD) is the accumulation of misfolded amyloid-β (Aβ) peptide. Several studies linked AD with type 2 diabetes due to similarities between Aβ and human amylin. This study investigates the effect of amylin and pramlintide on Aβ pathogenesis and the predisposing molecular mechanism(s) behind the observed effects in TgSwDI mouse, a cerebral amyloid angiopathy (CAA) and AD model. Our findings showed that thirty days of intraperitoneal injection with amylin or pramlintide increased Aβ burden in mice brains. Mechanistic studies revealed both peptides altered the amyloidogenic pathway and increased Aβ production by modulating amyloid precursor protein (App) and γ-secretase levels in lipid rafts. in addition, both peptides increased levels of B4GALNT1 enzyme and GM1 ganglioside, and only pramlintide increased the level of GM2 ganglioside. Increased levels of GM1 and GM2 gangliosides play an important role in regulating amyloidogenic pathway proteins in lipid rafts. increased brain Aβ burden by amylin and pramlintide was associated with synaptic loss, apoptosis, and microglia activation. In conclusion, our findings showed amylin or pramlintide increase Aβ levels and related pathology in tgSwDi mice brains, and suggest that increased amylin levels or the therapeutic use of pramlintide could increase the risk of AD.Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by multiple dysregulated neurobiological networks and cellular functions, neuronal death, and memory loss 1 . The major hallmarks for AD include amyloid-β (Aβ) deposits and neurofibrillary tangles of hyper-phosphorylated tau protein 1,2 . Aβ is produced from the amyloid-β precursor protein (APP), which, after synthesis, traffics to the Golgi apparatus and eventually to plasma membrane 3 . The majority of plasma membrane bound APP is rapidly endocytosed 3 , while approximately 10% of the total APP is processed in the plasma membrane by α-secretase to release soluble APP-α (sAPP-α) 4 . Alternatively, APP can be processed by β-site APP cleaving enzyme 1 (BACE1) in plasma membrane, trans-Golgi, and early endosomes to produce soluble APP-β (sAPP-β) and β-C-terminal fragments (β-CTF), followed by subsequent proteolytic cleavage of β-CTF by γ-secretase to release Aβ 4 . Besides Aβ production, another contributing factor to Aβ accumulation in AD is the failure to clear Aβ from the brain 5 , and across the blood-brain barrier (BBB) 6 .The accumulation of Aβ due to decreased clearance or increased production leads to multiple dysregulated cellular functions including synaptic loss and neuroinflammation 7,8 . Aβ initiates synaptic loss by down-regulating synaptic markers in AD including the pre-synaptic marker SNAP-25 and synapsin I and post-synaptic marker PSD-95 9 . Moreover, the accumulation of Aβ in the brain parenchyma of AD patients is associated with strong inflammatory processes and glial cells activation 7 .Mounting evidence supports the localization of APP, BACE1 and each of the four core subu...

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Extra-virgin olive oil attenuates amyloid-β and tau pathologies in the brains of TgSwDI mice

Cited by 86 publications

References 63 publications

Extra-virgin olive oil ameliorates cognition and neuropathology of the 3xTg mice: role of autophagy

Extra-virgin olive oil ameliorates cognition and neuropathology of the 3xTg mice: role of autophagy

Extra virgin olive oil improves synaptic activity, short‐term plasticity, memory, and neuropathology in a tauopathy model

Amylin and pramlintide modulate γ-secretase level and APP processing in lipid rafts

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