The accumulation of amyloid-beta (Aβ) and tau protein in the brain are the main two features of Alzheimer’s disease. But why do they start to accumulate and to harm our brain are still the questions to answer.
Aβ is not harmful in itself and can also be found in healthy people. However, it tends to assemble into toxic structures, oligomers, when the internal biochemical processes (such as metabolic processes) in the brain are disrupted. You can see toxic oligomers as the “smaller relatives” of Aβ protein. They are also accumulations of Aβ, but on a much smaller scale, typically comprising just a few units. So far, it was unclear where and how these oligomers form.
Now a recent study has found that a slightly acidic environment promotes the development of Alzheimer’s disease. In this environment, the oligomers form around 8.000 times quicker than in an environement with a neutral pH. Such a slightly decreased pH also can be found in certain substructures of nerve cells known as endosomes and lysosomes that look like small bubbles.
According to the study, endosomes and lysosomes are the sites at which Aβ oligomers are preferably formed in the first place (through the breakdown of a precursor protein). They are also assembly points to which Aβ is transported after being absorbed from the cell. The amounts of Aβ found in the regions of endosomes and lysosomes turned to be sufficient to enable the formation of Aβ oligomers.
The researchers were also able to establish a link between the toxic Aβ oligomers and tau protein. After adding the Aβ oligomers, they observed an erroneous distribution of the tau protein within the nerve cells. The tau protein in the wrong locations can lead to disruptions to the activity and structure of the nerve cells that result in loss of their function and the cognitive decline in people with Alzheimer’s.
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