Alzheimer’s disease (AD) is a degenerative brain disease that causes various cognitive impairments involving processes such as reasoning and memory. Typically, symptoms of AD begin appearing when individuals are in their mid-60s. AD interferes with a person’s daily behavioral abilities and is one of the leading causes of death in the United States. As a result, a significant amount of research focuses on studying the mechanisms that underly AD, including genetic and environmental risk factors. Despite conducting so much research regarding AD, much of it is not entirely applicable to many at-risk populations. For example, being a woman increases the risk of AD, but men are more represented in AD research. Similarly, it has been suggested that the mechanisms underlying AD differ by race. Yet, the majority of AD research is conducted with Caucasian participants.
In “Harnessing Genetic Complexity to Enhance Translatability of Alzheimer’s Disease Mouse Models: A Path toward Precision Medicine” by Kaczorowski et al., researchers incorporate genetic diversity into mouse models of AD to test their hypothesis that it would improve translational potential. To accomplish this goal and create mice models that would have the same high-risk mutations that humans could have, they combined a genetically diverse reference panel with an already existing established mouse model of AD. From the study, researchers conclude that human AD mutations are significantly influenced by genetic variation.
Kaczorowski et al. also discuss the APOE gene in their research paper, a gene that is already confirmed to play a role in AD. According to the paper, APOE increases AD symptoms because it causes an increase in the number of amyloid plaques. Further research is still being done on the role of APOE in AD. Further research into APOE can lead to understandings that help in detecting AD earlier in patients. Doing so can potentially lead to methods that can help lessen the severity and progression of AD symptoms.
As mentioned earlier, research in AD mostly represents AD as it presents in White males. Recent research suggests that the APOE gene and possibly the mechanisms underlying AD overall may operate differently in Black people. A difference in the process of AD based on race is leading to a difference in treatment of AD based on race. Research on tau protein buildup suggests that African American people have less tau buildup while still suffering from AD. As a result, Black people are more likely to wait until more advanced stages of AD before they start seeking medical care for their symptoms. The study described in this article found no differences in amyloid levels based on race.
Differences in an APOE gene variant, APOE4, were found based on race, however. While APOE4 confers a higher risk of AD in White people, it is not as dangerous for Black people. This is because Black people with the APOE4 variant seem to have much lower levels of tau protein buildup. As a result, lower levels of tau protein exposure would lead to lesser AD-related neurological damage. This leads to the inference that the mechanisms that underly AD may be different based on race. So, AD occurs more often in Black Americans even though the gene itself has relatively more benign effects. This again is one of the reasons why Black people are more likely to wait until more advanced stages of AD to seek medical care. Further research will allow healthcare providers to better care for Black patients with AD.
Some researchers hypothesize that tau protein may be accumulated differently in the brains of Black people compared to White people because of genetic differences in combination with environmental factors such as the chronic stress caused by racism. Some neurologists note that there may be inflammatory responses in the brain that could lead to different responses of tau buildup. Additionally, since lower levels of tau protein buildup suggest that Black people would have less neurological damage caused by AD, Black people with lower levels of tau may be even more responsive to newer drugs being developed that attack amyloid instead, since this tends to aggregate in the brain before tau does. To better care for people of different genetic and environmental backgrounds, a more diverse research methodology and participant inclusion need to be accounted for in AD research.
Thus, research studies that focus on high-risk mutations and genetic risk factors such as the Kaczorowski et al. study to enhance the translatability of AD models furthers the progression of research towards a more inclusive and accurate understanding of AD with respect to both its underlying mechanisms and effects. The effect of race on AD progression, both relating to its genetic and environmental components, should be significantly more incorporated into research study designs about AD to provide better care for individuals with different genetic and environmental backgrounds.
Citations:
Neuner SM, Heuer SE, Huentelman MJ, O'Connell KMS, Kaczorowski CC. Harnessing Genetic Complexity to Enhance Translatability of Alzheimer's Disease Mouse Models: A Path toward Precision Medicine. Neuron. 2019 Feb 6;101(3):399-411.e5. doi: 10.1016/j.neuron.2018.11.040. Epub 2018 Dec 27. PMID: 30595332; PMCID: PMC6886697.
Weintraub, K. (2019, January 08). Alzheimer’s attack on the brain may vary with race. Retrieved March 05, 2021, from https://www.scientificamerican.com/article/alzheimers-attack-on-the-brain-may-vary-with-race/
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