For decades, many people concerned about Alzheimer's disease have focused their attention on amyloid beta (Aβ)
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Through the microscope, it can be seen that there are special "plaques" in the patient's brain, the main component of which is amyloid fibrils composed of a large amount of Aβ
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According to the Aβ theory and the support of many research evidences, small-scale aggregates composed of a small amount of Aβ, namely Aβ oligomers, are very toxic to nerve synapses and are the only cause of Alzheimer’s disease.
The main toxic substances
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Recently, a research team in Germany explored the formation conditions of Aβ oligomers
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They found that weakly acidic conditions will accelerate the formation of such toxic oligomers, and in certain substructures in nerve cells, the presence of such a low pH environment may be a potential target to prevent the formation of Aβ oligomers.
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Research results show that the formation of Aβ oligomers is closely related to pH
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Compared with neutral conditions, the formation rate of Aβ oligomers is increased by 8000 times in weakly acidic conditions
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Such weakly acidic conditions can be found in the endosomes and lysosomes of neurons
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Endosomes and lysosomes are two small vesicle structures in cells, which play a key role in the process of material transport and degradation
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In the past research, endosomes and lysosomes have been regarded as one of the research focuses of Alzheimer's disease, because this is the main place for the formation of single Aβ molecules and the absorption of Aβ monomers for assembly
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"Now, our results show that endosomes and lysosomes are also places where Aβ oligomers are preferentially formed
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" The study's co-corresponding author Professor Wolfgang Hoyer explained
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In addition to acidic pH to enhance aggregation, the Aβ concentration in these regions is another important factor in the formation of oligomers
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▲Endosomes and lysosomes are the key sites that affect Aβ assembly in cells (picture source: reference [1])
The researchers also observed that with the increase of toxic Aβ oligomers, the mislocalization of another protein, tau, appeared in nerve cells, a protein closely related to the progression of Alzheimer's disease
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▲Aβ oligomer (picture source: reference [2]; Credit: Forschungszentrum Jülich, HHU Düsseldorf / Wolfgang Hoyer)
In addition, the research team analyzed the size and composition of Aβ oligomers through cryo-EM and AFM
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Note: The original text has been deleted
Reference materials:
[1] Marie P.
Schützmann et al.
, (2021) Endo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce Tau missorting.
[2] New insights into the formation of toxic protein clumps in Alzheimer's disease.
Retrieved Aug.
13, 2021 from https://medicalxpress.
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