Cross‐seeding between Aβ40 and Aβ42 in Alzheimer's disease

Tran, Joyce; Chang, Dennis; Hsu, Frederick; Wang, Hongsu; Guo, Zhefeng

doi:10.1002/1873-3468.12526

Cited by 43 publications

(42 citation statements)

References 52 publications

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“…Other groups have reported no detectable seeding of Aβ40 by Aβ42 fibrils, possibly due to differences in cross‐seeding efficiency for different Aβ42 fibril polymorphs, or due to other differences in experimental conditions. Cross‐seeding between Aβ40 and Aβ42 in both directions has been observed in some experiments …”

Section: Resultscontrasting

confidence: 64%

“…Cross-seeding between Ab40 and Ab42 in both directions has been observed in some experiments. 51 Depletion of Ab42 from solution by Ab40 seeds may occur by addition of Ab42 molecules to the ends of the Ab40 fibril fragments, resulting in individual fibrils that contain Ab40 and Ab42 in separate segments. Alternatively, Ab40 seeds may provide surfaces for heterogeneous nucleation of pure Ab42 fibrils.…”

Section: Experiments In Phosphate Buffer At 248cmentioning

confidence: 99%

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Depletion of amyloid‐β peptides from solution by sequestration within fibril‐seeded hydrogels

Yau

Tycko

2018

Protein Science

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Aggregation of amyloid-β (Aβ) peptides in brain tissue leads to neurodegeneration in Alzheimer's disease (AD). Regardless of the kinetics or detailed mechanisms of Aβ aggregation, aggregation can only occur if Aβ concentrations exceed their local equilibrium solubility values. We propose that excess Aβ peptides can be removed from supersaturated solutions, including solutions in biological fluids, by the addition of hydrogels that are seeded with Aβ fibril fragments. Fibril growth within the hydrogels then sequesters excess peptides until equilibrium concentrations are reached. Experiments with 40- and 42-residue Aβ peptides (Aβ40 and Aβ42) in phosphate buffer at 24°C and in filtered fetal bovine serum at 37°C, using crosslinked polyacrylamide hydrogels, demonstrate the validity of this concept. Aβ sequestration in fibril-seeded hydrogels (or other porous media) may prove to be a useful technique in experiments with animal models of AD and may represent a possible approach to preventing or slowing the progression of AD in humans.

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Section: Resultscontrasting

confidence: 64%

Section: Experiments In Phosphate Buffer At 248cmentioning

confidence: 99%

Depletion of amyloid‐β peptides from solution by sequestration within fibril‐seeded hydrogels

Yau

Tycko

2018

Protein Science

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“…Ab1-40 accumulates in the AD brain, but the extent of Ab1-40 accumulation relative to Ab1-42 is highly variable. It has been shown that Ab1-40 can promote Ab42 aggregation in a concentration-dependent manner (Tran et al, 2017). High Ab1-40 monomeric/Ab1-42 fibrillar ratios ($10) accelerate Ab fibril formation and the accumulation of fibrillar aggregates in the brain.…”

Section: Discussionmentioning

confidence: 99%

Honokiol Ameliorates Amyloidosis and Neuroinflammation and Improves Cognitive Impairment in Alzheimer’s Disease Transgenic Mice

Wang

Dong

Wang

2018

J Pharmacol Exp Ther

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The present study examined the effects of honokiol on amyloid- (A)-induced cognitive impairment and the underlying mechanisms in APPswe/PS1dE9 transgenic mice. The results showed that honokiol administration (20 mg/kg per day, intraperitoneally) for 6 weeks effectively improved spatial memory deficits in APPswe/PS1dE9 transgenic mice. Honokiol significantly lowered A production and senile plaque deposition by downregulating -site amyloid precursor protein cleavage enzyme 1 and enhancing A phagocytosis by microglia. Honokiol reduced glial cell activation and the production of proinflammatory cytokines (TNF-, IL-1, and IL-6). Honokiol increased the transcriptional activity and protein levels of peroxisome proliferator-activated receptor- (PPAR However, all of the beneficial effects of honokiol on pathologic changes, including biochemistry and cognitive function, could be blocked by GW9662, a specific PPAR inhibitor. These findings suggested that honokiol may be a natural PPAR agonist, acting to attenuate A generation and neuroinflammation. Therefore, honokiol may be a potential therapeutic approach for Alzheimer's disease.

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“…The Ser26Glu mutation was detected in the Aβ peptide (a message from S. Linse at the Amyloid 2019 conference in Lund), which does not lead to cross-seeding, which means that the structures from which the fibrils are built for the wild type and mutant shape are different (Tran et al, 2017). From the point of view of existing structures, such a mutation should not affect the fibril structure in any way, since in both structures of 2016 and 2017, this residue looks at the solvent (Wälti et al, 2016;Gremer et al, 2017).…”

Section: Why Do Not Mice Get Alzheimer's Disease? a Possible Organizamentioning

confidence: 99%

Oligomers Are Promising Targets for Drug Development in the Treatment of Proteinopathies

Galzitskaya

2020

Front. Mol. Neurosci.

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Currently, there is no effective treatment of proteinopathies, as well as their diagnosis in the early stages of the disease until the first clinical symptoms appear. The proposed model of fibrillation of the Aβ peptide and its fragments not only describes molecular rearrangements, but also offers models of processes that occur during the formation of amyloid aggregates. Since this model is also characteristic of other proteins and peptides, a new potential target for drug development in the treatment of Alzheimer's disease (AD) and other proteinopathies is proposed on the basis of this model. In our opinion, it is oligomers that are promising targets for innovative developments in the treatment of these diseases.

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Cross‐seeding between Aβ40 and Aβ42 in Alzheimer's disease

Cited by 43 publications

References 52 publications

Depletion of amyloid‐β peptides from solution by sequestration within fibril‐seeded hydrogels

Depletion of amyloid‐β peptides from solution by sequestration within fibril‐seeded hydrogels

Honokiol Ameliorates Amyloidosis and Neuroinflammation and Improves Cognitive Impairment in Alzheimer’s Disease Transgenic Mice

Oligomers Are Promising Targets for Drug Development in the Treatment of Proteinopathies

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