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Potential medicine for Alzheimer’s

Livia Civitella by the microscope

Alzheimer’s disease is a catastrophic diagnosis that invariably leads to death. A study at Linköping University now singles out a new candidate for a medicine: a molecule that can get through the blood-brain barrier and reduce the toxicity in the substance associated with the disease.

The p-FTAA molecule is a variant of the fluorescent conjugated polymer developed by Linköping researchers for purposes such as detecting the protein amyloid beta in the brain. When this occurs, they signal by changing colours – a change that can be measured with various technologies.

Now a team of experimental pathologists and biochemists have taken the molecule designated p-FTAA a step further.

“If you have substances that can bind this effectively to amyloid beta, you should also investigate if they can alter the toxicity,” says Katarina Kågedal, who – together with fellow senior lecturer Ann-Christin Brorsson – is publishing the results in the Journal of Biological Chemistry.

The role of amyloid beta in Alzheimer’s disease has been much debated. The substance occurs in several forms, of which the first – amyloid precursor protein, or APP – is important for communication between cells. From this basic form, amyloid beta arises in various forms such as monomeres, oligomeres, and – ultimately – fibrous aggregates, or plaque, that is hard to dissolve. Most researchers are now of the opinion that it is a transitional form – the oligomere – that plays the crucial role in the inexorable breakdown of nerve cells and of memory loss that affects patients. Reducing the level of these oligomeres could be one way of checking the progress of the disease.

The toxicity of amyloid beta was measured in a model with human nerve tumor cells. When p-FTAA was added, the equilibrium shifted so that the toxic amyloid beta oligomeres decreased, and at the same time the propensity of amyloid beta to spread in the sample was restricted. This could mean that p-FTAA can put a brake on the spread of Alzheimer’s pathology in the brain.

“Our study makes p-FTAA hotter for both diagnosis and treatment. A cocktail with various medicines – anti-inflammatory substances, for example – is conceivable,” says Ms Brorsson.

Today, over 120,000 people in Sweden are living with an Alzheimer’s diagnosis, which makes it our most common dementia-related illness. Since old age is the greatest risk factor, we can expect a constant increase of the illness in pace with a rising average lifespan.

Picture: Livia Civitelli, principal research engineer, has done a large part of the laboratory work behind the publication. The microscope image shows fibrils of amyloid beta.

Article: “The luminescent oligothiophene p-FTAA converts toxic Aβ1-42 species into nontoxic amyloid fibers with altered properties” by Livia Civitelli, Linnea Sandin, Erin Nelson, Sikander Igbal Khattak, Ann-Christin Brorsson and Katarina Kågedal. Journal of Biological Chemistry, February 2016, doi: 10.1074/jbc.M115.696229

 


Åke Hjelm Fri Apr 01 08:01:00 CEST 2016



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