Differences in biomarkers in people with genetic risk of Alzheimer’s – study


A large study of indicators in the blood suggests differences in people at genetic risk of Alzheimer’s disease.

The research found associations of neuro-inflammatory and cholesterol biomarkers in people with a genetically high risk of Alzheimer’s.

The most common form of dementia is believed to be the result of interactions between genetic and environmental risk factors, and the Alzheimer’s disease (AD) susceptibility gene – Apolipoprotein e4 (APOE e4) – is a major genetic risk factor.

One copy of the gene is found in around 25% of the population, increasing risk of dementia by at least three times.

Two copies are found in around 2% of the population, increasing risk by around 15 times, researchers say.

APOE e4 is the largest common single genetic risk factor for Alzheimer’s and cognitive decline, behind increasing age.

Published in the Journal of Alzheimer’s Disease, the study used data from nearly 400,000 people in the UK Biobank.

Researchers looked at a wide range of blood biomarkers – such as cholesterols, markers of inflammation, vitamin D and IGF-1 levels (insulin growth factor), sex-specific hormones and renal function – in people carrying the APOE e4 genotype.

They found that a previously suggested risk factor of a low IGF-1 level, based on studies including people diagnosed with the disease, might be the opposite, with a raised IGF-1 level a potential risk factor.

Previous studies reported an association between APOE e4 and higher vitamin D levels, but this study found decreased levels of vitamin D, suggesting higher levels could be protective for people at risk of Alzheimer’s.

Dr Donald Lyall, lecturer in public health at the University of Glasgow’s Institute of Health and Wellbeing and senior author on the study, said: “Our research confirmed that the APOE e4 genotype predicted subsequent dementia.

“But, more importantly, by looking at such a large sample size and such a wide range of biomarkers – both in patients with the disease and those currently non-demented but at high genetic risk – we were able to get a ‘big picture’ look at the role of common biomarkers and this gene, which is considered to be dementia-causing.

“Our findings of relatively large associations between e4 genotype with neuro-inflammatory biomarkers and elevated cholesterol levels reinforces that these biological pathways are important to our understanding of common, late-onset Alzheimer’s disease.

“While these findings could suggest biomarkers for dementia, further studies are needed to fully determine their role in dementia, both in those with a high genetic risk for Alzheimer’s disease and more generally.”

The study looked at data from 395,769 participants of white European ancestry.