Health
Some Alzheimer's cases may be caused by copies of a single gene, research shows
- Researchers have identified a genetic form of late-in-life Alzheimer’s disease for the first time, which occurs in people inheriting two copies of the APOE4 gene.
- APOE4 is known to increase the risk of Alzheimer’s.
- Symptoms in those with two APOE4 copies can manifest seven to ten years earlier compared to those with other risk factors.
For the first time, researchers have identified a genetic form of late-in-life Alzheimer’s disease — in people who inherit two copies of a worrisome gene.
Scientists have long known a gene called APOE4 is one of many things that can increase people’s risk for Alzheimer’s, including simply getting older. The vast majority of Alzheimer’s cases occur after age 65. But research published Monday suggests that for people who carry not one but two copies of the gene, it’s more than a risk factor, it’s an underlying cause of the mind-robbing disease.
The findings mark a distinction with “profound implications,” said Dr. Juan Fortea, who led the study the Sant Pau Research Institute in Barcelona, Spain.
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Among them: Symptoms can begin seven to 10 years sooner than in other older adults who develop Alzheimer’s.
For the first time, researchers have identified a genetic form of late-in-life Alzheimer’s disease — in people who inherit two copies of a worrisome gene. (AP Photo/David Duprey, File)
An estimated 15% of Alzheimer’s patients carry two copies of APOE4, meaning those cases “can be tracked back to a cause and the cause is in the genes,” Fortea said. Until now, genetic forms of Alzheimer’s were thought to be only types that strike at much younger ages and account for less than 1% of all cases.
Scientists say the research makes it critical to develop treatments that target the APOE4 gene. Some doctors won’t offer the only drug that has been shown to modestly slow the disease, Leqembi, to people with the gene pair because they’re especially prone to a dangerous side effect, said Dr. Reisa Sperling, a study coauthor at Harvard-affiliated Brigham and Women’s Hospital in Boston.
Sperling hunts ways to prevent or at least delay Alzheimer’s and “this data for me says wow, what an important group to be able to go after before they become symptomatic.”
But the news doesn’t mean people should race for a gene test. “It’s important not to scare everyone who has a family history” of Alzheimer’s because this gene duo isn’t behind most cases, she told The Associated Press.
HOW DO GENETICS AFFECT ALZHEIMER’S?
More than 6 million Americans, and millions more worldwide, have Alzheimer’s. A handful of genes are known to cause rare “early-onset” forms, mutations passed through families that trigger symptoms unusually young, by age 50. Some cases also are linked to Down syndrome.
But Alzheimer’s most commonly strikes after 65, especially in the late 70s to 80s, and the APOE gene – which also affects how the body handles fats — was long known to play some role. There are three main varieties. Most people carry the APOE3 variant that appears to neither increase nor decrease Alzheimer’s risk. Some carry APOE2, which provides some protection against Alzheimer’s.
APOE4 has long been labeled the biggest genetic risk factor for late-in-life Alzheimer’s, with two copies risker than one. About 2% of the global population is estimated to have inherited a copy from each parent.
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To better understand the gene’s role, Fortea’s team used data from 3,297 brains donated for research and from over 10,000 people in U.S. and European Alzheimer’s studies. They examined symptoms and early hallmarks of Alzheimer’s such as sticky amyloid in the brain.
People with two APOE4 copies were accumulating more amyloid at age 55 than those with just one copy or the “neutral” APOE3 gene variety, they reported in the journal Nature Medicine. By age 65, brain scans showed significant plaque buildup in nearly three-quarters of those double carriers – who also were more likely to have initial Alzheimer’s symptoms around that age rather than in the 70s or 80s.
Fortea said the disease’s underlying biology was remarkably similar to young inherited types.
It appears more like “a familial form of Alzheimer’s,” said Dr. Eliezer Masliah of the National Institute on Aging. “It is not just a risk factor.”
Importantly, not everyone with two APOE4 genes develops Alzheimer’s symptoms and researchers need to learn why, Sperling cautioned.
“It’s not quite destiny,” she said.
HOW THE NEW FINDINGS MAY AFFECT ALZHEIMER’S RESEARCH AND TREATMENT
The drug Leqembi works by clearing away some sticky amyloid but Sperling said it’s not clear if carriers of two APOE4 genes benefit because they have such a high risk of a side effect from the drug – dangerous brain swelling and bleeding. One research question is whether they’d do better starting such drugs sooner than other people.
Masliah said other research aims to develop gene therapy or drugs to specifically target APOE4. He said it’s also crucial to understand APOE4’s effects in diverse populations since it’s been studied mostly in white people of European ancestry.
As for gene tests, for now they’re typically used only to evaluate if someone’s a candidate for Leqembi or for people enrolling in Alzheimer’s research – especially studies of possible ways to prevent the disease. Sperling said the people most likely to carry two APOE4 genes had parents who both got Alzheimer’s relatively early, in their 60s rather than 80s.
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Study finds link between obesity and vascular dementia
Fox News senior medical analyst Dr. Marc Siegel joins ‘America’s Newsroom’ to discuss an increase in colon cancer in people under 50 despite an overall lowering cancer deaths and a new study linking obesity to vascular dementia.
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A new blood test could determine a woman’s dementia risk as early as 25 years before symptoms emerge.
That’s according to new research from the University of California San Diego, which found that a specific biomarker protein associated with early pathological processes of Alzheimer’s disease was “strongly linked” to future dementia risk.
The researchers analyzed blood samples from 2,766 participants in the Women’s Health Initiative Memory Study in the late 1990s, according to the study’s press release.
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The women ranged from 65 to 79 years of age and showed no signs of cognitive decline at the start of the study.
After tracking the participants for up to 25 years, the researchers concluded that the biomarker phosphorylated tau 217 (p-tau217) was “strongly associated” with future mild cognitive impairment and dementia.
A new blood test could determine a woman’s dementia risk as early as 25 years before symptoms emerge. (iStock)
Women who had higher levels of p-tau217 at the beginning of the study were “much more likely” to develop the disease. The findings were published today in JAMA Network Open.
“The key takeaway is that our study suggests it may be possible to detect risk of dementia two decades in advance using a simple blood test in older women,” first author Aladdin H. Shadyab, a UC San Diego associate professor of public health and medicine, told Fox News Digital.
“These biomarkers may help us identify who is at greatest risk and develop strategies to delay or prevent dementia.”
“Our findings show that the blood biomarker p-tau217 could help identify individuals at higher risk for dementia long before symptoms begin,” he added.
This long lead time could open the door to earlier prevention strategies and more targeted monitoring, rather than waiting until memory problems are already affecting daily life, according to Shadyab.
A specific biomarker protein associated with early pathological processes of Alzheimer’s disease was “strongly linked” to future dementia risk. (iStock)
“As the research advances, these biomarkers may help us identify who is at greatest risk and develop strategies to delay or prevent dementia,” he said.
This risk relationship wasn’t the same across the board, however. Women over 70 with higher p-tau217 levels had “poorer cognitive outcomes” compared to those under 70, as did those with the APOE ε4 gene, which is a known risk factor for Alzheimer’s disease.
The study also found that p-tau217 was a stronger predictor of dementia in women who were randomly assigned to receive estrogen and progestin hormone therapy compared to those who received a placebo.
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“Blood-based biomarkers like p-tau217 are especially promising because they are far less invasive and potentially more accessible than brain imaging or spinal fluid tests,” said senior author Linda K. McEvoy, senior investigator at Kaiser Permanente Washington Health Research Institute and professor emeritus at the Herbert Wertheim School of Public Health, in the release.
“Blood-based biomarkers like p-tau217 are especially promising because they are far less invasive and potentially more accessible than brain imaging or spinal fluid tests,” a researcher said. (iStock)
“This is important for accelerating research into the factors that affect the risk of dementia and for evaluating strategies that may reduce risk.”
Blood tests for Alzheimer’s disease are still being studied and are not recommended for routine screening in people without symptoms, Shadyab noted.
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More research is needed before this approach can be considered for clinical use prior to cognitive symptoms.
Future studies should investigate how other factors — like genetics, hormone therapy and age-related medical conditions — might interact with plasma p-tau217, the researchers added.
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“The study examined only older women, so the findings may not necessarily apply to men or younger populations,” Shadyab noted. “We also examined overall dementia outcomes rather than specific subtypes such as Alzheimer’s disease.”
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For women over 60, muscle strength plays a critical role in longevity, a new study confirms.
Researchers at the University at Buffalo, New York, followed more than 5,000 women between the ages of 63 and 99, finding that those with greater muscle strength had a significantly lower risk of death over an eight-year period.
The findings were published in JAMA Network Open.
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Muscle function was measured using grip strength and how quickly participants could complete five unassisted sit-to-stand chair raises.
These are two tests commonly used in clinical settings to evaluate muscle function in older adults, the researchers noted.
A recent study shows that stronger muscle strength in women over 60 is linked to a lower risk of death over eight years. (iStock)
“In a community cohort of ambulatory older women, muscular strength was associated with significantly lower mortality rates, even when we accounted for usual physical activity and sedentary time measured using a wearable monitor, gait speed and blood C-reactive protein levels,” study lead author Michael LaMonte, research professor of epidemiology and environmental health at the University at Buffalo, told Fox News Digital.
“Movement is the key — just move more and sit less.”
Many earlier studies did not include those objective measurements, making it difficult to determine whether muscle strength itself was linked to longevity, according to LaMonte. “Our study was able to better isolate the association between strength and death in later life,” he added.
Even for women who don’t get the recommended amount of aerobic physical activity, which is at least 150 minutes per week, muscle strength remained important for longevity, the researchers found.
Women with greater muscle strength were more likely to live longer, even if they did not meet the recommended amount of aerobic exercise. (iStock)
“The findings of lower mortality in those who had higher strength but were not meeting current national guidelines on aerobic activity were somewhat intriguing,” LaMonte said.
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Federal guidelines recommend strengthening activities one to two days per week, targeting major muscle groups.
Resistance training does not have to require a gym membership, LaMonte noted. These exercises can be performed using free weights, resistance bands, bodyweight movements or even household items, such as soup cans.
Experts recommend working major muscle groups one or two days a week using weights, bands or bodyweight exercises. (iStock)
“Movement is the key — just move more and sit less,” he said. “When we can no longer get out of the chair and move around, we are in trouble.”
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LaMonte acknowledged several limitations of the study. The researchers assessed muscle strength in older age but did not explore how earlier levels in adulthood might influence long-term health outcomes.
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“We were not able to understand how strength and mortality relate in younger ages,” he said, noting that future research should explore whether building strength earlier could have an even greater impact on longevity.
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