Biomarker in the blood affects the risk of dementia

In a new major genetic study, researchers from Rigshospitalet, Herlev and Gentofte Hospital, and the University of Copenhagen have shown that low apolipoprotein E levels in the blood have a causal relationship with the risk of developing dementia.
A total of 47 million people worldwide suffer from dementia – in Denmark alone around 84,000 people live with the disease. The incidence of dementia increases in line with age, and since life expectancy is constantly increasing in most countries, the incidence of dementia is expected to increase significantly over the coming years. 

Currently, there is no medical cure for dementia. Consequently, finding the biological components that have a direct causal relationship with dementia is vital. Development of new medicine can then be targeted at the molecules that directly cause the disease. 

- We've identified a marker in the blood which is very likely to reflect processes in the brain and therefore is likely to be part of the cause of dementia, said Ruth Frikke-Schmidt, Consultant, MD at Rigshospitalet and Clinical Research Associate Professor at the Faculty of Health and Medical Sciences, University of Copenhagen. 

The research project was conducted collaboratively with Katrine Laura Rasmussen, MD and PhD at Rigshospitalet as well as Herlev and Gentofte Hospital, Professor Anne Tybjærg-Hansen, Consultant and MD at Rigshospitalet, and Professor Børge G. Nordestgaard, Consultant and MD at Herlev and Gentofte Hospital.

More than 100,000 blood samples tested

In order to investigate a possible causal relationship between apolipoprotein E levels and dementia, the researchers examined blood and DNA from 106,562 subjects from the Copenhagen General Population Study (Herlev-Østerbroundersøgelsen) and the Copenhagen City Heart Study (Østerbroundersøgelsen).

The researchers examined the participants' DNA for the presence of five genetic variants that were strongly linked to apolipoprotein E levels in the blood. The analysis showed that the presence of genetic variants demonstrating low apolipoprotein E levels also increased the risk of developing dementia.

- We've shown that people with life-long low apolipoprotein E levels in the blood caused by genetic variation also have an increased risk of developing dementia. As genetic variants are not affected by other risk factors or diseases, this is a clean result which can help us determine causal relationships. The findings make biological sense, as apolipoprotein E is a central molecule in removing β-amyloid; the sticky substance of which the senile plaques in dementia are composed. When apolipoprotein E levels in the brain are low, removal of β-amyloid is less efficient. This is a likely explanation for the increased risk of dementia, explained Ruth Frikke-Schmidt.

- Our findings underline that this strategy of examining the causal relationship between a marker in the blood and a disease – in this case apolipoprotein E in the blood and dementia – is an important method to support development of new, effective medicines. New medicines will only be effective if they directly affect a component with a causal relationship with the disease. If the molecules at which a new medicine is targeted do not directly cause the disease, the medicine will not be effective, or at worst it may cause damage, said Ruth Frikke-Schmidt.  

How do patients benefit from these findings?

Better knowledge about the biological causes of dementia can help target development of new, effective medicines. As the incidence of dementia will increase significantly over the next few years, it is vital to prevent the disease as well as develop effective medicines.

Research funding

The research project was funded by the Danish Council for Independent Research | Medical Sciences, Rigshospitalet's Research Committee, the Lundbeck Foundation and Alzheimer-Forskningsfonden (Danish Alzheimer's research foundation).

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