Summary: Researchers identified key risk factors and genetic influences impacting a specific brain network vulnerable to aging, schizophrenia, and Alzheimer’s disease. This ‘weak spot’ in the brain is especially susceptible to diabetes, air pollution, and alcohol consumption.
By examining 161 modifiable risk factors in over 40,000 individuals, the study highlights the importance of a comprehensive approach to understanding dementia’s complexities. Intriguingly, the research also uncovered a connection to the XG blood group antigens and genes shared by both X and Y chromosomes, opening new avenues for genetic exploration in dementia.
Key Facts:
- Vulnerable Brain Network: This study pinpoints a brain network that is crucially impacted by aging and diseases such as schizophrenia and Alzheimer’s, showing increased susceptibility to specific lifestyle and environmental factors.
- Top Risk Factors Identified: Among the modifiable risk factors examined, diabetes, traffic-related air pollution, and alcohol consumption were found to have the most significant impact on the brain’s vulnerable network.
- Genetic Insights Revealed: The research uncovered genetic associations with dementia, including links to cardiovascular disease and the XG blood group system, highlighting underexplored areas of the genome.
Source: University of Oxford
The researchers had previously identified a ‘weak spot’ in the brain, which is a specific network of higher-order regions that not only develop later during adolescence, but also show earlier degeneration in old age.
They showed that this brain network is also particularly vulnerable to schizophrenia and Alzheimer’s disease.
In this new study, published in Nature Communications, they investigated the genetic and modifiable influences on these fragile brain regions by looking at the brain scans of 40,000 UK Biobank participants aged over 45.
The researchers examined 161 risk factors for dementia, and ranked their impact on this vulnerable brain network, over and above the natural effects of age.
They classified these so-called ‘modifiable’ risk factors – as they can potentially be changed throughout life to reduce the risk of dementia – into 15 broad categories: blood pressure, cholesterol, diabetes, weight, alcohol consumption, smoking, depressive mood, inflammation, pollution, hearing, sleep, socialisation, diet, physical activity, and education.
Prof. Gwenaëlle Douaud, who led this study, said: ‘We know that a constellation of brain regions degenerates earlier in aging, and in this new study we have shown that these specific parts of the brain are most vulnerable to diabetes, traffic-related air pollution – increasingly a major player in dementia – and alcohol, of all the common risk factors for dementia.’
‘We have found that several variations in the genome influence this brain network, and they are implicated in cardiovascular deaths, schizophrenia, Alzheimer’s and Parkinson’s diseases, as well as with the two antigens of a little-known blood group, the elusive XG antigen system, which was an entirely new and unexpected finding.’
Prof. Lloyd Elliott, a co-author from Simon Fraser University in Canada, concurs: ‘In fact, two of our seven genetic findings are located in this particular region containing the genes of the XG blood group, and that region is highly atypical because it is shared by both X and Y sex chromosomes.
‘This is really quite intriguing as we do not know much about these parts of the genome; our work shows there is benefit in exploring further this genetic terra incognita.’
Importantly, as Prof. Anderson Winkler, a co-author from the National Institutes of Health and The University of Texas Rio Grande Valley in the US, points out: ‘What makes this study special is that we examined the unique contribution of each modifiable risk factor by looking at all of them together to assess the resulting degeneration of this particular brain ‘weak spot’.
‘It is with this kind of comprehensive, holistic approach – and once we had taken into account the effects of age and sex – that three emerged as the most harmful: diabetes, air pollution, and alcohol.’
This research sheds light on some of the most critical risk factors for dementia, and provides novel information that can contribute to prevention and future strategies for targeted intervention.
About this Alzheimer’s disease and genetics research news
Author: Christopher McIntyre
Source: University of Oxford
Contact: Christopher McIntyre – University of Oxford
Image: The image is credited to Neuroscience News
Original Research: Open access.
“The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease” by Gwenaëlle Douaud et al. Nature Communications
Abstract
The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease
We have previously identified a network of higher-order brain regions particularly vulnerable to the ageing process, schizophrenia and Alzheimer’s disease.
However, it remains unknown what the genetic influences on this fragile brain network are, and whether it can be altered by the most common modifiable risk factors for dementia.
Here, in ~40,000 UK Biobank participants, we first show significant genome-wide associations between this brain network and seven genetic clusters implicated in cardiovascular deaths, schizophrenia, Alzheimer’s and Parkinson’s disease, and with the two antigens of the XG blood group located in the pseudoautosomal region of the sex chromosomes.
We further reveal that the most deleterious modifiable risk factors for this vulnerable brain network are diabetes, nitrogen dioxide – a proxy for traffic-related air pollution – and alcohol intake frequency.
The extent of these associations was uncovered by examining these modifiable risk factors in a single model to assess the unique contribution of each on the vulnerable brain network, above and beyond the dominating effects of age and sex.
These results provide a comprehensive picture of the role played by genetic and modifiable risk factors on these fragile parts of the brain.
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