Researchers at the University of Glasgow have conducted the largest study to date on a wide range of common blood biomarkers and show clear differences in people at genetic risk of Alzheimer’s disease.
The research – published in the Journal of Alzheimer’s Disease – used data from nearly 400,000 people in the UK Biobank and found relatively-large associations of neuro-inflammatory and cholesterol biomarkers, such as low-density lipoprotein levels, in people with a genetically-high risk of Alzheimer’s disease.
Alzheimer’s disease is the most common form of dementia, and is believed to be the result of interactions between genetic and environmental risk factors.
The Alzheimer’s disease (AD) susceptibility gene – apolipoprotein e4 (ApoE ε4) – is a major genetic risk factor for the disease, with one copy of the gene found in around 25% of the population, increasing risk of dementia by at least three times. Two copies of the gene are found in around 2% of the population, increasing risk of dementia by around 15 times. ApoE ε4 is the largest common single genetic risk factor for AD and cognitive decline behind increasing age.
The study aimed to investigate the potential influence of ApoE ε4 on common blood biomarkers, while also taking into account lifestyle factors, in both people with confirmed AD and those at a genetically-high risk for the disease.
The researchers looked at a wide range of blood biomarkers – such as cholesterols, markers of inflammation, vitamin D and IGF-1 levels, sex-specific hormones and renal function -- in people carrying the APOE ε4 genotype (compared with the ‘neutral’ ε3 carriers) to better understand the mechanisms of AD and dementia risk.
The research also found that a previously suggested risk factor of a low IGF-1 level, based on studies including people diagnosed with AD, might in fact be the opposite, with a raised IGF-1 level a potential risk factor. Previous studies also reported an association between ApoE ε4 and higher vitamin D levels; however, this study found decreased levels vitamin D, suggesting higher levels could be protective for people at risk for AD.
Dr Donald Lyall, (Lecturer in Public Health at the University’s Institute of Health and Wellbeing and senior author on the study, said: “Our research confirmed that the ApoE ε4 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 ε4 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.