Research on Alzheimer’s has mainly focused on Caucasians. New findings, however, suggest the disease process that leads to dementia may differ in African-Americans. According to a study published in January in JAMA Neurology, the brains of African-Americans diagnosed with Alzheimer’s have less buildup of a protein called tau—one of the two hallmark proteins that characterize the disease. It is not clear why African-Americans would have less tau while still suffering from Alzheimer’s, says neurologist John Morris, who led the research. But the finding is significant because it means the medical community needs to exercise caution when defining Alzheimer’s by measures of tau buildup alone. The study also suggests race might affect other aspects of the disease’s pathology, says Morris, who directs the Knight Alzheimer Disease Research Center at Washington University in Saint Louis. “The study of Alzheimer’s disease, which really began formally in the United States in the mid-1980s, has largely been of white people,” he notes. “The U.S. in general and the older adult portion of the U.S. population is increasingly diverse, so we really do need to study all populations to try to understand the disease and its forms.” For the moment, the differences detected in the disease’s pathology will not change existing treatment protocols, which do not yet look at certain aberrant proteins to make a diagnosis. Physicians today diagnose Alzheimer’s largely based on a patient’s neuropsychological characteristics. But once researchers have developed a more practical way to measure levels of key proteins involved in the disease, such differences could be crucial for accurate diagnoses, Morris says. Brain scans can detect tau as well as amyloid beta—another protein that builds up in the brains of Alzheimer’s sufferers—but the scans are expensive and not widely available. The study found no racial difference in amyloid levels. African-American study participants, though, had a much lower concentration of tangled clumps of the tau protein, whether or not they had dementia. The research looked at 1,255 people—some with Alzheimer’s, some cognitively normal—including 173 African-Americans. The study also found that a variant of a gene called APOE4, which confers a high risk of Alzheimer’s in whites, seemed to be less of a peril for African-Americans. The latter tended to have much lower tau levels if they had the APOE4 variant, suggesting they suffered less neurological damage because of the lesser tau exposure. “The mechanism may be different in African-Americans than it is in whites,” Morris says. Alzheimer’s occurs more often in black Americans, even if the gene itself is more benign. Morris says some blacks may be more likely to wait until advanced stages of the disease before seeking medical care. Other research has suggested APOE4 provides some protection against infectious diseases including malaria, and that the gene is more common in people whose ancestors came to the U.S. from tropical climates where those diseases are more frequent. Among the Saint Louis study participants, African-Americans were just as likely to have the APOE4 gene as were Caucasians. But in an earlier study in Atlanta that also looked at tau and APOE4, black Americans with dementia were far more likely to carry APOE4. African-Americans had lower levels of tau in both studies. Tau may accumulate differently in the brains of African-Americans because of genetic differences between the races or because of the chronic stress of racism and other factors, notes William Hu, a neurologist and researcher at Emory University School of Medicine who led the earlier study. It is unclear what the mechanism might be, but African-Americans are known to have a different response to inflammation than whites, he says. “There may be a different inflammatory response that would lead to a different tau-based response.” In the new research, tau was measured in cerebrospinal fluid. Patients also underwent PET brain scans to measure amyloid buildup, MRIs to gauge brain volume, genetic testing for APOE4 status and other clinical evaluations. “This is a critically important study as we move toward the goal of individualized medicine,” Hu says. If lower levels of the tau protein mean a patient has less Alzheimer’s-related damage to the brain, as research suggests, African-Americans with these relatively low levels might be more responsive to drugs that are being developed to attack amyloid, Hu says. Amyloid tends to aggregate before tau in the disease process. These regional research efforts, Hu says, should spur a nationwide study that examines how race affects various aspects of disease progression. Such a study, he adds, should be designed with a proportionally higher number of black participants to make the findings statistically valid. The race a person checks off on a form is a crude biological measure. Eventually, he says, this type of study will define groups by genetic makeup rather than self-described race to account for the many individuals of mixed heritage. Morris also urges more investigation to understand how Alzheimer’s acts in diverse groups of people. “I hope this publication will stimulate the need for our research efforts to become more welcoming to people of color,” he says, “and not settle for enrolling individuals who are fairly easy to enroll: upper-class whites.” Keith Fargo, the director of scientific programs and outreach for the Alzheimer’s Association, says the study is a reminder that measuring protein levels in the brain and other advances should not be used yet in physicians’ offices until they are better understood. “It’s a good idea to continue to measure these biomarkers in all different kinds of people—and not get too far ahead of ourselves in terms of clinical practice,” he says.
It is not clear why African-Americans would have less tau while still suffering from Alzheimer’s, says neurologist John Morris, who led the research. But the finding is significant because it means the medical community needs to exercise caution when defining Alzheimer’s by measures of tau buildup alone. The study also suggests race might affect other aspects of the disease’s pathology, says Morris, who directs the Knight Alzheimer Disease Research Center at Washington University in Saint Louis. “The study of Alzheimer’s disease, which really began formally in the United States in the mid-1980s, has largely been of white people,” he notes. “The U.S. in general and the older adult portion of the U.S. population is increasingly diverse, so we really do need to study all populations to try to understand the disease and its forms.”
For the moment, the differences detected in the disease’s pathology will not change existing treatment protocols, which do not yet look at certain aberrant proteins to make a diagnosis. Physicians today diagnose Alzheimer’s largely based on a patient’s neuropsychological characteristics. But once researchers have developed a more practical way to measure levels of key proteins involved in the disease, such differences could be crucial for accurate diagnoses, Morris says. Brain scans can detect tau as well as amyloid beta—another protein that builds up in the brains of Alzheimer’s sufferers—but the scans are expensive and not widely available.
The study found no racial difference in amyloid levels. African-American study participants, though, had a much lower concentration of tangled clumps of the tau protein, whether or not they had dementia. The research looked at 1,255 people—some with Alzheimer’s, some cognitively normal—including 173 African-Americans.
The study also found that a variant of a gene called APOE4, which confers a high risk of Alzheimer’s in whites, seemed to be less of a peril for African-Americans. The latter tended to have much lower tau levels if they had the APOE4 variant, suggesting they suffered less neurological damage because of the lesser tau exposure. “The mechanism may be different in African-Americans than it is in whites,” Morris says. Alzheimer’s occurs more often in black Americans, even if the gene itself is more benign. Morris says some blacks may be more likely to wait until advanced stages of the disease before seeking medical care.
Other research has suggested APOE4 provides some protection against infectious diseases including malaria, and that the gene is more common in people whose ancestors came to the U.S. from tropical climates where those diseases are more frequent. Among the Saint Louis study participants, African-Americans were just as likely to have the APOE4 gene as were Caucasians. But in an earlier study in Atlanta that also looked at tau and APOE4, black Americans with dementia were far more likely to carry APOE4. African-Americans had lower levels of tau in both studies.
Tau may accumulate differently in the brains of African-Americans because of genetic differences between the races or because of the chronic stress of racism and other factors, notes William Hu, a neurologist and researcher at Emory University School of Medicine who led the earlier study. It is unclear what the mechanism might be, but African-Americans are known to have a different response to inflammation than whites, he says. “There may be a different inflammatory response that would lead to a different tau-based response.”
In the new research, tau was measured in cerebrospinal fluid. Patients also underwent PET brain scans to measure amyloid buildup, MRIs to gauge brain volume, genetic testing for APOE4 status and other clinical evaluations. “This is a critically important study as we move toward the goal of individualized medicine,” Hu says.
If lower levels of the tau protein mean a patient has less Alzheimer’s-related damage to the brain, as research suggests, African-Americans with these relatively low levels might be more responsive to drugs that are being developed to attack amyloid, Hu says. Amyloid tends to aggregate before tau in the disease process.
These regional research efforts, Hu says, should spur a nationwide study that examines how race affects various aspects of disease progression. Such a study, he adds, should be designed with a proportionally higher number of black participants to make the findings statistically valid. The race a person checks off on a form is a crude biological measure. Eventually, he says, this type of study will define groups by genetic makeup rather than self-described race to account for the many individuals of mixed heritage.
Morris also urges more investigation to understand how Alzheimer’s acts in diverse groups of people. “I hope this publication will stimulate the need for our research efforts to become more welcoming to people of color,” he says, “and not settle for enrolling individuals who are fairly easy to enroll: upper-class whites.”
Keith Fargo, the director of scientific programs and outreach for the Alzheimer’s Association, says the study is a reminder that measuring protein levels in the brain and other advances should not be used yet in physicians’ offices until they are better understood. “It’s a good idea to continue to measure these biomarkers in all different kinds of people—and not get too far ahead of ourselves in terms of clinical practice,” he says.
