- A new study finds a gene known as APOE is a major risk factor for Alzheimer’s disease for certain demographic groups
- They found the risk was strongest for white individuals and for older women.
- APOE genes are not the sole determinant — or even the major determinant — of whether one develops Alzheimer’s disease, experts said.
New research has shed light on how specific genetic variants impact a person’s risk of Alzheimer’s disease, based on demographic factors like their sex and ethnicity.
According to prior evidence, a gene known as apolipoprotein E (APOE) is a major genetic risk factor for Alzheimer’s disease (AD) and different forms of APOE have different effects.
APOE*2, for example, is known to be protective against AD and APOE*4 increases the risk for late-onset Alzheimer’s disease.
The new report, published in JAMA Neurology on Monday, found that the relationship between APOE*2 or APOE*4 and the risk for Alzheimer’s disease was strongest amongst white individuals, less strong amongst Black individuals, and weakest amongst Hispanic individuals.
“The main takeaway here is that the risk for developing Alzheimer’s disease seems to be related, at least in part, to a complex relationship between genetics and demographic characteristics,” Dr. Leah Croll, an assistant professor of clinical neurology at the Lewis Katz School of Medicine at Temple University and a neurologist at Temple University Hospital, told Healthline. Croll was not involved in the study.
The link between APOE and AD risk differs by race and sex
The researchers evaluated the health and genetic data of 68,756 individuals, which included 21,852 East Asian, 5,738 Hispanic, 7,145 Black, and 34,021 white individuals.
Race and ethnicity were self-reported by participants.
The researchers evaluated the relationship between AD risk and various APOE genotypes across age, sex, race and ethnicity.
They found that the association between APOE genotypes, both APOE*2 and APOE*4, with AD risk was the strongest within white people and the least pronounced among Hispanic individuals.
There was no association between APOE*2 and AD among Hispanic and East Asian individuals.
There was, however, a protective effect when East Asian and Hispanic individuals had both APOE*2 and APOE*4 genotypes.
Within Black individuals, decreased global African ancestry or increased global European ancestry showed a pattern where APOE*4 dosage was associated with increasing AD risk.
“These findings suggest that ancestry and ethnicity play an important role in modulating our genetic risk for Alzheimer’s disease, but there is still so much we don’t know about this,” says Croll.
The researchers also investigated how sex impacts the association between APOE genotypes and AD risk.
They found that, among white individuals ages 60 to 70 with the APOE*34 genotype, the risk for Alzheimer’s daises was higher in women.
“The contribution of APOE genotype to an individual’s risk of developing AD with aging varies based on the race and ethnicity of the individual. The authors also found greater risk among women,” said Dr. David Merrill, MD, PhD, a geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center in Santa Monica, CA. Merrill was not involved in the study.
APOE genotypes may help inform future studies and treatment
In general, APOE*4 increases a person’s lifetime risk of developing AD whereas APOE*2 lowers that risk.
An estimated 66% of individuals with biologically-defined AD carry at least one APOE*4 allele, research shows.
“These APOE genetic variants are less common than the APOE*3 allele carried by 75% of individuals, which confers about a 10% lifetime risk of developing AD,” said Merrill.
Prior research has suggested that sex, race and ethnicity, and population ancestry affect how different APOE genotypes impact the risk of AD, but the interactions have been unclear.
In addition, past evidence suggests Hispanic individuals may be more likely to develop dementia than other demographic groups, according to Croll.
“So, it is interesting to see that the genes we most associate with Alzheimer’s risk don’t seem to have as big an impact in this group,” she said.
APOE genes are not the sole determinant — or even the major determinant — of whether one develops AD, Merrill added.
There are many modifiable lifestyle risk factors that can lower the risk of developing AD.
“It’s interesting to know which modifiable risks are most important to address in those with APOE*4 genes,” Merrill said.
The report could inspire future research to investigate what makes certain groups of people more vulnerable than others and help guide treatment options.
“The more we learn in this space, the more we will be able to offer patients the most effective treatments for them as individuals,” Croll said.
The bottom line:
New research has shed light on how specific genetic variants impact a person’s risk of Alzheimer’s disease, based on demographic factors like their sex and ethnicity. The findings could inspire future research to investigate what makes certain groups of people more vulnerable than others and help guide treatment options.
This Genetic Variant Raises the Risk for Alzheimer's Disease, Who is Most at Risk
Source: Pinoy Lang Sakalam
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