First author Dr Abbas Dehghan, Principal Scientist at the UK DRI at Imperial, explained:
“From genetic studies, we know that the ABCA7 gene is associated with an increased risk of Alzheimer’s, but until now we haven’t known why. Our study indicates that genetic variations in the gene are linked to altered levels of a type of molecule called lactosylceramide in the blood. This suggests that lactosylceramides and the pathways they are involved in may be one of the missing links between the ABCA7 gene and increased risk of Alzheimer’s.”
With further analysis, the researchers discovered a potential causal link between lactosylceramide levels in the blood, and an increased risk of Alzheimer’s – suggesting that the ceramide pathway contributes towards risk of developing the disease.
As the blood is separated from the brain by the blood brain barrier, the researchers also wanted to test whether their findings could be replicated inside the brain. To investigate this, they used a mouse model where the ABCA7 gene had been deleted to help understand its role. They found that lactosylceramide levels were altered in the brains of the mice, showing that ABCA7 is involved in regulating lactosylceramide levels within the brain as well as in the blood.
Prof Paul Elliott, Group Leader at the UK DRI at Imperial, and Head of the Department of Epidemiology and Biostatistics at Imperial College London, and leader of the study, said:
“The number of people affected by Alzheimer’s disease is growing as the population ages, but unfortunately, there are currently very limited treatment options. Our study is an important step closer to understanding the underlying mechanisms of Alzheimer’s, which could aid in the development of new drugs to treat the condition.
“Armed with this new information about the potential role of lactosylceramides in Alzheimer’s, we plan to undertake further investigations, to try to understand how changes in this and other pathways may lead to the development of the disease.”
Prof Jules Griffin, Director of the Rowett Institute at the University of Aberdeen, a co-investigator on the study, said:
“Our research is important for two reasons. Firstly, we outline why people with changes in the gene sequence of ABCA7 are predisposed to developing Alzheimer’s disease. Secondly, this work highlights that ceramides, a special kind of fat, or lipid, important for our cells to function correctly, may play a key role in the development of Alzheimer’s. If we understand this better, we could develop new treatments and lifestyle interventions to reduce the impact of the disease.
“This study has defined the role of lactosylceramide and highlighted how important this pathway may be in Alzheimer’s disease, something that has been largely overlooked until now.”
To find out more about Prof Elliott's work, visit his UK DRI profile. To stay up to date on the latest research news and Institute updates, sign up to receive our monthly newsletter, ‘Inside Eye on UK DRI'.
Article published: 24 October 2022
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