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Scientists identify the risks of Alzheimer's disease depending on genetic variants

7.02.2020
The scientists from Banner Alzheimer’s Institute and Arizona Alzheimer’s Consortium, (USA) analyzed the risks of developing Alzheimer's disease (AD) depending on the particular variant in the APOE gene.
Alzheimer's disease is the most widespread type of dementia which is characterized by progressive loss of memory and cognitive function due to degeneration of synapses and axons. According to WHO statistics for 2019 there are about 50 million people with dementia worldwide. It is considered that AD is a multifactorial disease that develops under the influence of many causes. Genetic predisposition is one of them. Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer’s dementia, while the APOE2 allele is associated with a lower risk of Alzheimer’s dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk.
The researchers have analyzed the impact of discovering and targeting the mechanism by which APOE variants account for differential risk could have on the understanding, treatment, and prevention of AD.
They discover that persons with the APOE2/2 genotype had a 66% lower OR than those with the APOE2/3 genotype, 87% lower than those with the APOE3/3 genotype, and 99.6% (95% CI: 98.6–99.9%) lower than those with APOE4/4 group. These findings highlight the impact of APOE and its variants on the risk of AD and the potential impact of APOE-modifying interventions on its treatment and prevention.
“Additional research is needed to clarify the mechanisms by which homozygosity for APOE2 and APOEch are associated with an exceptionally low risk of AD dementia. Gene editing, protein-reducing, protein-modifying, or other treatments that safely and sufficiently replicate protective effects of the APOE2/2 genotypes could help to prevent the clinical onset of AD.”


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