Diabetes Masks Alzheimer’s Biological Changes in the Brain
Research led by King’s College London suggests diabetes may mask biological changes linked to Alzheimer’s disease, raising the possibility that the underlying biology of Alzheimer’s differs between people with and without diabetes.
Diabetes is a major risk factor for Alzheimer’s disease, and the two conditions share several biological processes, including mitochondrial dysfunction, inflammation, oxidative stress and impaired insulin signalling. This suggests that diabetes may contribute to the progression of changes in the brain associated with Alzheimer’s disease.
The paper, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, examined mitochondrial DNA copy number (mtDNA-CN) in post-mortem samples from three regions of the human brain: the hippocampus, amygdala and cerebellum.
The team found that Alzheimer’s disease and diabetes were associated with opposing changes in mitochondrial DNA. Alzheimer’s was associated with lower mtDNA-CN, while diabetes was associated with higher levels across all three brain regions.
When people with diabetes were removed from the analysis, mtDNA-CN was 19 to 30 per cent lower in people with Alzheimer’s compared with cognitive controls. In contrast, among people with Alzheimer’s, those with diabetes had significantly higher mtDNA-CN than those without diabetes. Levels were 41 per cent higher in the hippocampus, 52 per cent higher in the amygdala and 64 per cent higher in the cerebellum. Surprisingly, all diabetes cases, including those with and without dementia, had higher mtDNA in these three regions than non-diabetic controls.
These opposing effects suggest that including people with diabetes in Alzheimer’s studies could reduce or mask differences associated with Alzheimer’s itself.
The findings suggest that diabetes may change the way Alzheimer’s disease is associated with mitochondrial changes, rather than simply being a background health condition. This could mean that the relationship between Alzheimer’s and mitochondrial DNA may be different in people with diabetes compared with those without diabetes.
“The key finding of our study in relation to Alzheimer’s disease is that grouping both diabetic and non-diabetic data for mtDNA-CN together can result in loss of real changes which may be important in disease mechanisms. Our research supports the growing view that Alzheimer’s disease can affect people in different ways at a biological level, and that conditions such as diabetes may contribute to these differences.”
Senior author Dr Afshan Malik
“We were surprised to find that mtDNA-CN was higher in the brains of people with diabetes. We don’t yet know whether this represents a response to cellular stress, a compensatory mechanism, or something else and what this means for the brain function. Our next step is to use multi-omics approaches to understand the biological consequences of this change and how it may affect brain function.”
First author Dr Aakruti Kaikini
The study provides a possible explanation for why previous studies of mitochondrial dysfunction in Alzheimer’s disease have produced conflicting results, potentially making it more difficult to diagnose patients.
In the future the researchers hope the results could be important for developing better ways to identify and understand Alzheimer’s disease, tailoring treatments to individual patients and designing future dementia clinical trials.
Source: King’s College London
