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The largest study to date on the topic used data from nearly 400,000 people in the UK Biobank.

Researchers at the University of Glasgow’s Institute of Health and Wellbeing have announced they have found people with genetic risk of Alzheimer’s disease exhibiting clear differences in certain biomarkers.

It supports a link between a major genetic risk factor and blood cholesterol levels. The risk factor APOE e4, which is present in a quarter of the population and triples the risk of

dementia, could possibly be the key to future early diagnosis and treatment. The 2% of the

population with a double copy have a 15 times higher risk of developing the disease.

The team investigated associations between common blood biomarkers and apolipoprotein E (APOE), a known genetic risk factor for Alzheimer’s disease, to improve understanding of disease mechanisms and risk. 

The study reviewed anonymised data from nearly 400,000 White European participants of the UK Biobank, a public health database, including lifestyle data in their analysis to account for the impact of environmental factors. Using a linear regression analysis to test correlation, they found that risk factor APOE e4 corresponded with elevated low-density lipoprotein cholesterol (LDL) and the “protective” genotype e4 with lower LDL in line with previous studies. High levels of low-density lipoprotein cholesterol are associated with poor cardiovascular health.

However, associations found in this study between APOE e4 and biomarkers such as vitamin D (calciferol) and the antibodies insulin-like growth factor unexpectedly opposed the trends identified in earlier research.

The biomarker differences were also present in people at genetic risk for dementia, but who were not showing symptoms.

Further research is required to investigate the mechanisms of interaction between the genetic risk factor and highlighted biomarkers that cause the disease.

Linear regression produces a “least squares” best fit line such that the sum of all the residuals is a minimum. To produce an accurate result, the inputs must be independent – not including multiple observations on the same individual – and exclude extreme outliers. Even if regression analysis suggests strong association, the accuracy of the result depends on the quality of the model used.

Alzheimer’s disease is the most common form of dementia. Common symptoms for the neurodegenerative disease include progressive loss of memory and higher-level thinking ability, but the underlying causes are still unclear. Other prevalent forms of dementia include vascular dementia, which is brain cell death caused by damage to the network of capillaries that oxygenate the brain and Lewy body dementia, which presents similarly to Alzheimer’s disease. The Alzheimer’s Society estimates that around 850,000 people in the UK have dementia.

In a statement to the University's news page, lead author Dr Amy Ferguson expressed hope that an increased understanding of such biomarkers among those at risk of Alzheimer’s disease would lead to early diagnosis and potentially options for intervention. Dr Ferguson also cautioned that further investigation was needed to clarify their role in dementia among populations with and without a genetic risk of the disease.

The study features White European participants predominantly due to their majority in the sample; blood groups and biomarkers vary markedly across regional genetic groups, so this allows consistency among the data analysed.

Data for the study was sourced from the UK Biobank, a database comprising anonymised medical records, vital statistics, full body scans, and lifestyle information for its 500,000 volunteers. Opened to vetted researchers in 2012, the database is linked to registers for deaths and diseases, and aims to present a comprehensive picture of lifetime personal and community health in England, Wales, and Scotland.Research was published on Tuesday 18 August 2020 in the Journal of Alzheimer’s Disease.


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