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Inhibiting protein production potentially a weapon against Alzheimer’s

Inhibiting specific protein production in the human body can serve as a crucial weapon in the fight against Alzheimer's, Eline van Maanen believes. PhD defence 23 November.

Alzheimer's disease is the most common form of dementia: seventy per cent of all those who suffer from dementia have Alzheimer's. The condition is starting to reach epidemic proportions as a result of the ‘double ageing’ factor. Fortunately, more and more is gradually being discovered about how the disease progresses, offering perspectives for the development of treatments.

Protein production

PhD candidate Eline van Maanen shows in her dissertation that inhibiting the production of a particular specific protein in the human body may contribute to the prevention of the disease. This makes it possible to prevent so-called toxic oligomers from accumulating between the nerve cells, which reduces communication between the brain cells and causes forgetfulness.

'Misfolding'

‘Until recently it was assumed that the main culprits were plaques; accumulations of agglomerated proteins,’ says Van Maanen. ‘However, the disease’s development may start much earlier, namely with the "misfolding" of the so-called beta-amyloid proteins. Normally the body destroys misfolded proteins, but sometimes that goes wrong. Those misfolded proteins then clump together to form toxic oligomers, which in turn form the plaques. The first mistakes often occur twenty to thirty years before the first symptoms.’

Mathematical model

In her research, Van Maanen showed, among other things, that lowering the protein concentration in the nervous system does indeed lead to reduced accumulation of oligomers. She demonstrated this by creating a mathematical model with which she could examine the data from existing animal experiments. She specifically studied the role of two enzymes (BACE1 and GS) that are important in the production of beta-amyloid proteins.

Other findings

Another important finding from Van Maanen’s study was that inhibition of the formation of beta-amyloid proteins led to oligomers separating on their own, boosting the effect of medication. The PhD candidate also discovered that, within the various beta-amyloid proteins, only the Aβ42 variant leads to toxic oligomers.