People who possess the gene ApoE4 and have chronic low-grade inflammation have an elevated risk of developing Alzheimer’s disease, according to a new study from researchers at the Boston University School of Medicine.
The scientists’ findings could help doctors prevent carriers of the ApoE4 gene from developing the disease, according to the study, which was published Oct. 19.
The study is the result of decades of data collection and consistent participant involvement. The researchers studied the brain volume of 2,656 eligible patients, considered diagnoses of incident dementia, and measured levels of C-reactive protein (CRP), which serves as a measure of chronic low-grade inflammation.
The data came from the Framingham Heart Study, which is run in part by the BUSM and the School of Public Health, said Charles DeCarli, a corresponding author of the study and director of the Alzheimer’s Disease Center, a research center funded by the United States National Institutes of Health.
The combination of the ApoE4 gene carried by each patient and significant CRP levels indicated an increased risk of Alzheimer’s, according to the study.
DeCarli said the risk factors the researchers identified could be a significant step forward in Alzheimer’s prevention.
“[Reducing inflammation] may not do anything once you have Alzheimer’s disease,” DeCarli said, “but it may be a good identifier for things that could be treated ahead of time that in the long run may improve [patients’] brain health, and therefore they won’t develop the syndrome of dementia. It’s all about prevention in this case.”
In light of the study’s findings, doctors should more aggressively treat inflammation in ApoE4 carriers, said Wendy Wei Qiao Qiu, a professor of psychiatry and pharmacology at BUSM.
Alzheimer’s disease is the sixth leading cause of death in the United States, affecting an estimated 5.7 million Americans, and is projected to affect up to 14 million by 2050, according to the Alzheimer’s Association.
Being able to target certain populations based on specific genetic vulnerabilities is a more effective approach to conducting clinical trials, said Qiu, who was a corresponding author on the study.
“This study is suggesting to me that if you see ApoE2 or ApoE3 carriers, it really doesn’t matter if they have chronic low-rate inflammation, especially ApoE2 carriers, it doesn’t affect them,” Qiu said. “However, if you have ApoE4, especially ApoE4 homozygous, it’s dangerous to Alzheimer’s disease development.”
Future clinical trials should focus on populations with this genetic vulnerability, Qiu said.
A challenge to Alzheimer’s research cited by both DeCarli and Qiu is that the natural aging process of people is a curveball in identifying early markers for Alzheimer’s development.
“This ApoE4 genotype, which is a susceptibility to Alzheimer’s disease, is also a gene that’s susceptible to brain injury from other causes,” DeCarli said.
Understanding the causes and risk factors for Alzheimer’s can be difficult, Qiu said, but this study “puts a piece of the puzzle there.”
Checking for the ApoE4 gene is easy, and testing CRP levels is common, Qiu said, so doctors can easily monitor patients for this risk factor.
Given the findings of this study, DeCarli said he believes further research should be conducted to understand the effect that the combination of CRP and ApoE4 has on brain health.
“Is there something unique about this combination that damages the brain that we could do something about?” DeCarli said. “Just simply reducing the systemic inflammation — will that be sufficient?”
Qiu also said she supports further research, citing the importance of conducting more clinical trials with different study samples to both reinforce the conclusion drawn from this study and to employ more effective medications against low-grade chronic inflammation.
“We should really see if this result, this data, can be replicable with other populations, especially in the clinical sense,” Qiu said. “We have to see which medication, based on ApoE status, will be effective to intervene or prevent the disease.”