In a new major study, researchers from the University of Copenhagen, Rigshospitalet as well as Herlev and Gentofte Hospital have found that genes which are strongly linked to low apolipoprotein E levels in the blood increase the risk of developing dementia.

Dementia is becoming increasingly widespread among Danes, and there is currently no medicine to cure the disease. It is therefore extremely important to find biological components with a direct causal relationship with dementia in order to target the development of new medicine at the molecules causing the disease.

The link between a biological component and dementia is being investigated in a new study from the University of Copenhagen, Rigshospitalet as well as Herlev and Gentofte Hospital, which was published in the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

“We show that people with permanent low apolipoprotein E levels in the blood caused by genetic variation are also at increased risk of developing dementia. Since genetic variants are not affected by other risk factors or diseases, this is a clean result which can help us establish causal relationships. The findings are biologically meaningful as this protein is a central molecule in removing the sticky substance which the senile plaques in dementia are composed of. When apolipoprotein E levels in the brain are low, removal of the sticky substance is less efficient, which is a likely explanation for the increased risk of dementia,” says Ruth Frikke–Schmidt, Clinical Research Associate Professor at the Faculty of Health and Medical Sciences, University of Copenhagen, and Consultant Doctor, MDSc at the Department of Clinical Biochemistry, Rigshospitalet. To study the potential causal relationship between apolipoprotein E levels and dementia, the researchers tested blood and DNA from 106,562 individuals from the Herlev–Østerbro study and the Østerbro study.

The researchers tested the participants’ DNA for the presence of five genetic variants strongly linked to the blood level of apolipoprotein E. The analysis showed that the presence of genetic variants with low apolipoprotein E levels also increased the risk of dementia.

“Our findings underline that this strategy of studying 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 of supporting the development of new, effective medicine. New medicine will only have an effect if it directly affects a component with a causal relationship with the disease. If the molecules at which the new medicine is targeted do not directly cause the disease, the medicine will not have an effect, or will – in worst case – cause damage,” said Ruth Frikke–Schmidt.

The research project was conducted in collaboration with Katrine Laura Rasmussen, Medical Doctor, PhD, Rigshospitalet and Herlev and Gentofte Hospital, Anne Tybjærg–Hansen, Professor, Consultant Doctor, DMSc, Rigshospitalet, and Børge G. Nordestgaard, Professor, Consultant Doctor, DMSc, Herlev and Gentofte Hospital. The project is funded by the Independent Research Fund Denmark | Medical Sciences, Rigshospitalet’s Research Committee and the Lundbeck Foundation.

The study is titled, “Plasma apolipoprotein E levels and risk of dementia – A Mendelian randomization study of 106,562 individuals.”