Identifying new medicines to treat Alzheimer’s Disease through greater understanding of the APOE gene.
Alzheimer’s disease (AD) is the most common form of dementia, responsible for at least 60% of cases. Today, there is a worldwide effort underway to find better ways to treat the disease, delay its onset and prevent it from developing. Although researchers have had some success in finding ways to delay the cognitive and functional decline in people living with early Alzheimer’s and improve the quality of life for sufferers and their caregivers, a cure is still out of reach.
The ADAPTED consortium spent 4 years researching the APOE gene to better understand it and create a model for the future development of Alzheimer Disease treatments. Here we will outline the findings of 3 of the papers published in the wake of this research.
It’s worth beginning by acknowledging the relevance of the APOE gene in relation to AD research. It is widely accepted that the APOE genotype is the strongest genetic risk factor for AD. A 2018 study published in The Lancet Neurology concluded that the identification of these genes, particularly APOEε4, could determine AD risk. Read more about this subject at https://www.sciencedirect.com/science/article/abs/pii/S147444221830053X?via%3Dihu
In a study published in May 2020 the researchers surmised that Apolipoprotein E (APOE) is the most common genetic risk factor for Alzheimer’s disease, and that APOE interacts with other common genetic determinants of AD suggesting an interaction with specific protein pathways. Interestingly they found that CDH6 protein is implicated in cell adhesion and synaptogenesis while HAGH protein is related to the oxidative stress pathway. Their findings suggest that these pathways may be altered during presymptomatic AD and that CDH6 and HAGH may be new blood-based biomarkers. Read the full article https://www.nature.com/articles/s41598-020-65038-5#Abs1
Another very interesting study of genome-wide meta-analysis shows a common genetic signature shared by heart function and AD. The study shows an unexpected potential genetic link between echocardiographic measures in healthy populations and cognitive decline in later life. These findings may be important in designing preventative strategies to combat Alzheimer’s disease. Read the paper https://www.nature.com/articles/s41598-019-52724-2
These are just a few of the publications resulting from the ADAPTED project, for a complete list visit the ADAPTED website.
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Ahmad, S., Milan, M.d.C., Hansson, O. et al. CDH6 and HAGH protein levels in plasma associate with Alzheimer’s disease in APOE ε4 carriers. Sci Rep 10, 8233 (2020). https://doi.org/10.1038/s41598-020-65038-5
Sáez, M.E., González-Pérez, A., Hernández-Olasagarre, B. et al. Genome Wide Meta-Analysis identifies common genetic signatures shared by heart function and Alzheimer’s disease. Sci Rep 9, 16665 (2019). https://doi.org/10.1038/s41598-019-52724-2
Sven J van der Lee, Frank J Wolters, M Kamran Ikram, A. et al. The effect of APOE and other common genetic variants on the onset of Alzheimer’s disease and dementia. The Lancet Neurology, 17, Issue 5(2018). https://doi.org/10.1016/S1474-4422(18)30053-X