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.
CAN WE REVERSE ALZHEIMER’S DISEASE? EXPERTS SUGGEST ‘NEW PARADIGM’ FOR COMBATING DEMENTIA
Among them: Symptoms can begin seven to 10 years sooner than in other older adults who develop Alzheimer’s.
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.
RESEARCH POINTS TO A CAUSE FOR A SUBSET OF ALZHEIMER’S
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.
Health
How Lagging Vaccination Could Lead to a Polio Resurgence
Most American parents hardly give thought to polio beyond the instant their child is immunized against the disease. But there was a time in this country when polio paralyzed 20,000 people in a year, killing many of them.
Vaccines turned the tide against the virus. Over the past decade, there has been only one case in the United States, related to international travel.
That could change very quickly if polio vaccination rates dropped or the vaccine were to become less accessible.
Robert F. Kennedy Jr., a longtime vaccine skeptic who may become the secretary of health and human services, has said the idea that vaccination has nearly eradicated polio is “a mythology.”
And while Mr. Kennedy has said he’s not planning to take vaccines away from Americans, he has long contended that they are not as safe and effective as claimed.
As recently as 2023, he said batches of an early version of the polio vaccine, contaminated with a virus, caused cancers “that killed many, many, many, many, many more people than polio ever did.” The contamination was real, but research never bore out a link to cancer.
Aaron Siri, a lawyer and adviser to Mr. Kennedy, has represented a client seeking to challenge the approval or distribution of some polio vaccines on the grounds that they might be unsafe.
Those efforts appear unlikely to succeed. And there is widespread support for vaccination among prominent Republicans, including President-elect Donald J. Trump and Senator Mitch McConnell, who had polio as a child.
But the secretary of health and human services has the authority to discourage vaccination in less direct ways. He or she could withdraw federal funds for childhood vaccination programs, hasten the end of school mandates in states already disinclined toward vaccines or fuel doubts about the shots, exacerbating a decline in immunization rates.
If polio vaccination rates were to fall, scientists say, the virus could slip into pockets of the country where significant numbers of people are unvaccinated, wreaking havoc once more. The virus may be nearly eradicated in its original form, but resurgence remains a constant threat.
Any decision the Trump administration makes regarding the polio vaccine is likely to ripple across the globe, said Dr. David Heymann, an infectious disease physician at the London School of Hygiene and Tropical Medicine and former leader of polio eradication at the World Health Organization.
“If the U.S. takes away the license, then many other countries will do the same thing,” he said. To have polio resurge when it is so close to eradication “would be very, very, very, very sad.”
Before 1955, when the vaccine was introduced, polio disabled more than 15,000 Americans each year and hundreds of thousands more worldwide. In 1952 alone, it killed 3,000 Americans after paralysis left them unable to breathe.
Many of those who survived still live with the consequences.
“People really underestimate how horrific polio was,” said Dr. Karen Kowalske, a physician and polio specialist at University of Texas Southwestern Medical Center in Dallas.
Many who recovered now suffer “post-polio syndrome”: Some of the original symptoms, including muscle weakness and respiratory problems, return.
Dr. Kowalske tends to about 100 post-polio patients who need braces, wheelchairs or other devices to cope with progressive weakness. Some are older adults who became infected before the vaccine was available; others are middle-aged immigrants from countries where polio remained a problem for much longer than in the United States.
To some survivors, the idea of polio’s return is unfathomable.
Carol Paulk contracted the disease in 1943, when she was just 3. Her right leg never recovered, and for the rest of her life she has walked with a pronounced limp and has been in near-constant pain.
Ms. Paulk is among the luckier ones. Until recently, she did not suffer the breathing, swallowing or digestive problems that often torment polio survivors.
She has had “a wonderful, wonderful life” with a husband and three daughters, a law degree and extensive travel abroad.
But always, everywhere, she is calculating how far away the next seat is, how long her energy will hold out and whether a given activity is worth debilitating pain the next day.
She didn’t participate in the 1963 March on Washington or play sports, as she desperately wanted to, or go hiking, skiing and bicycling with her husband.
If there were a public hearing about the polio vaccine now, “I would go, and I would take off my brace, and I would let them see my leg and ask them, is that what they want for their children?” she said.
Polio disables many fewer children now. Vaccination has scrubbed the virus from most of the planet, slashing the number of cases by more than 99.9 percent and preventing an estimated 20 million cases of paralysis.
Still, the virus has turned out to be a stubborn enemy, and eradication has been set back over and over again.
In 2024, 20 countries reported polio cases, and the virus was detected in wastewater in five European countries, decades after its official elimination from the region, and in Australia.
“Any reduction in coverage rates increases the risk of polio anywhere,” said Oliver Rosenbauer, a spokesman for the World Health Organization’s polio eradication program.
There are three types of polioviruses, and eradication requires that all three disappear. For years, the goal has been tantalizingly close.
Type 2 was declared vanquished in 2015, and Type 3 in 2019. Type 1 now circulates only in Afghanistan and Pakistan. In 2021, the two countries together had just five cases; in 2024, they had 93.
But those figures tell only part of the story. In a surprising twist, an oral vaccine used in some parts of the world has kept poliovirus circulating long after it should have died out.
In most low- and middle-income countries, health officials still rely on an oral vaccine given as two drops on the tongue. It is inexpensive and easy to administer, and it prevents transmission of the virus.
But it contains weakened virus, which vaccinated children can shed into the environment through their feces. When there are enough unvaccinated children to infect, the pathogen slowly spreads, regaining its virulence and eventually causing paralysis.
The problem is this: Since 2016, the oral vaccine used for routine immunization has not protected against Type 2 virus. Global health authorities made a deliberate decision to reformulate the vaccine on the grounds that naturally occurring Type 2 virus had disappeared.
That turned out to be premature. More Type 2 virus had been shed by orally vaccinated children in some parts of the world than officials had anticipated. When some nonimmunized children, or those given the newer oral vaccine, encountered this “vaccine-derived” Type 2 virus, they became infected and paralyzed.
Vaccine-derived poliovirus now paralyzes more children than naturally occurring virus does. For example, Nigeria eliminated all so-called wild-type polio in 2020. But in 2024, the country saw 93 cases of Type 2 vaccine-derived virus, more than one-third the global total.
None of this is a problem for Americans — as long as they are vaccinated.
The inactivated polio vaccine (I.P.V.) used for routine immunization of American children protects against all three types of polio. These formulations contain dead virus, and so cannot cause disease or revert to a dangerous form.
But like some other vaccines for infectious diseases, they do not fully prevent infection or transmission of the virus. This aspect is among the criticisms of Mr. Siri, Mr. Kennedy’s adviser.
Still, it is less important than the vaccines’ near-perfect power to prevent paralysis, experts said.
“Yeah, yeah, it’s true, I.P.V. doesn’t prevent transmission,” said Dr. William Petri, an infectious diseases physician and past president of the W.H.O.’s polio research committee. “But, boy, that’s the best thing since sliced bread at preventing paralysis.”
It does mean, however, that people vaccinated with I.P.V. can keep the virus circulating, even when they themselves are protected against illness and paralysis.
So here’s a realistic scenario that worries researchers: Someone who was vaccinated with the oral polio vaccine in another country might bring the virus into the United States and then shed it, in its weakened form. This has already happened in other countries.
So long as most of the population remains vaccinated, this is not likely to set off an epidemic. But if the virus makes its way into communities with low vaccination rates, it may spread, and then revert to a virulent form that can cause paralysis.
That is what happened in New York in 2022, when polio struck a 20-year-old unvaccinated member of an ultra-Orthodox Jewish community in Rockland County.
The vaccination rate in that county was just over 60 percent, compared with the national average of 93 percent.
The virus that paralyzed the young man had been circulating for months, and it was later detected in the sewage of multiple New York counties with vaccination rates hovering around 60 percent, prompting the state to declare an emergency.
Genetically related polioviruses were detected in wastewater samples in Britain, Israel and Canada, suggesting widespread transmission. The authorities later found two distinct vaccine-derived Type 2 polioviruses in New York wastewater, suggesting two separate importations.
If polio were to re-emerge in the United States, it is unlikely to be as horrific as it was in the pre-vaccine decades. Many older adults still remember that as children they were not permitted to swim in rivers or pools, or anywhere the virus might lurk.
“The reason we weren’t allowed to play in rivers in the ’50s is because raw sewage was dumped into the rivers,” Dr. Heymann said.
That is no longer the case, so there “wouldn’t be massive transmission immediately in the U.S.,” he added.
But even if just a few children were to become paralyzed, “it would be awful.”
Health
RFK Jr.’s MAHA Movement Obscures America’s Unhealthy Past
“We will make Americans healthy again,” Robert F. Kennedy Jr. has declared. A political action committee that has promoted Mr. Kennedy, President-elect Donald J. Trump’s pick for health and human services secretary, says his movement is “igniting a health revolution in America.”
But the word “again” presumes a time in the country’s past when Americans were in better health. Was there ever really a time when America was healthier?
For historians of medicine, there is a short answer.
“No,” said Nancy Tomes, a historian at Stony Brook University.
John Harley Warner, a historian at Yale, said, “It’s hard for me to think of a time when America, with all the real health disparities that characterize our system, was healthier.”
Dr. Jeremy Greene, a historian at Johns Hopkins University, asked: “Which particular era does R.F.K. want to take us back to?”
Probably not the 19th and early 20th century.
Rich men smoked cigarettes and cigars, the poor chewed tobacco. Heavy drinking was the norm.
“It was definitely a drinking culture,” said Dora Costa, an economic historian at the University of California, Los Angeles. “Drinking was a huge problem, saloons were a huge concern. Men were drinking away their paychecks. That is the reason we had Prohibition.”
And, Dr. Costa notes, American diets for most of the 19th century were monotonous.
It’s true that agriculture at the time was organic, food was locally produced and there were no ultraprocessed foods. But fresh fruits and vegetables were in short supply because they were difficult to ship and because growing seasons were so short. For the most part, Dr. Costa said, until the 1930s, “Americans were living off of dried fruits and vegetables.”
As for protein, Americans were relying on salted pork, she said, because meat was difficult to preserve. Only after the Civil War did meatpackers in Chicago begin to process meat and ship fresh beef across the country. At that point, Dr. Costa said, beef “became a large part of the American diet.”
But even though the availability of beef helped diversify diets, people did not become healthier.
Dr. Costa worked with Robert Fogel, the University of Chicago economic historian and Nobel laureate, to understand the health of a population of Americans living in the North around this period by examining the medical records of Union Army soldiers. Common conditions, like hernias, were untreatable — men had hernias as big as grapefruits, held in by trusses. Nineteen percent of those soldiers had heart valve problems by the time they were 60, compared with about 8.5 percent today.
Poor nutrition led to poor health. People were thin, often too thin. In 1900, 6.1 percent of Union Army veterans were underweight — a risk factor for various illnesses and often a marker of ill health — compared with 1.6 percent of U.S. adults today. In 1850, males at age 20 could expect to live to around 61 years. Today it is 74 years.
The start of the 20th century saw public health improvements (cleaner water, for example, and posters advising parents not to give their babies beer), but disease was rampant. There were no antibiotics and very few vaccines. When the 1918 flu struck the nation, no one knew the cause — the flu virus had not been discovered and strange folk remedies were rampant. About 675,000 Americans died. In 1929, the Great Depression began, and its economic toll over the next decade led to severe nutritional and health problems.
Health improved in the second half of the 20th century but was poor compared with that today.
Many people are nostalgic for the 1950s and 1960s, seeing those decades as a time of prosperity, when the American pharmaceutical industry pumped out new medical advances: antibiotics, antipsychotics, drugs for high blood pressure and vaccines for tetanus, diphtheria, measles and polio.
Despite that progress, those years were terrible for health, Dr. Greene said, with “a tremendous amount of heart attacks and strokes.”
Heart disease was rampant in 1950, with 322 deaths per 100,000 Americans annually from cardiovascular disease, double the rate today. By 1960, Dr. Greene said, heart disease, was responsible for one-third of all deaths in America.
In part, that was because nearly everyone smoked.
“We were among the heaviest smoking countries,” said Samuel Preston, an emeritus professor of sociology at the University of Pennsylvania.
Dr. David F. Musto, a medical historian at Yale, who died in 2010, once said in an interview that although he never enjoyed smoking, the social pressure to smoke when he was in college in the 1950s was so great that “I felt it was my duty to find my brand.”
Smoking greatly increases the risk for heart disease, the leading killer in the 1950s and 1960s.
Heart disease death rates plummeted in recent decades because smoking is much less common now, and treatment for heart disease is much more effective. Cholesterol-lowering statins, introduced in 1987, reduced the risk of heart disease. Other new medications as well as bypass surgery and stents also saved lives.
Cancer was the second leading killer in the 1950s, as it is today. But in 1950, there were 194 cancer deaths per 100,000 people. Now there are 142 cancer deaths per 100,000 people.
A decline in smoking is a leading reason, but there also has been a revolution in cancer treatment.
Until the 1990s, cancer was treated with brute force: surgery, radiation and chemotherapy. Now an array of targeted therapies are turning some cancers, once deadly, into treatable chronic diseases or even curing them.
Dr. Greene said he was not surprised by the idea of a halcyon past when people were healthier.
“There’s a long history in America of nostalgia for a past that was better than the present,” he said. “History is all about erasure — the things we don’t choose to remember.”
Today is not a sort of health utopia, of course.
Researchers are quick to acknowledge that Americans’ health is not as good as it can be. And they bemoan the huge disparities in health care in this country.
Yet the U.S. spends more on medical care than other countries — an average of $12,555 per capita, which is about twice what other wealthy countries spend.
But, historians say, the past was actually much worse.
And so, they say, the phrase “Make America Healthy Again” makes no sense.
“As a historian of health, I don’t know what ‘again’ Kennedy is imagining,” Dr. Tomes said. “The idea that once upon a time all Americans were healthy is a fantasy.”
Health
Childhood Vaccination Rates Were Falling Even Before the Rise of R.F.K. Jr.
After years of holding steady, American vaccination rates against once-common childhood diseases have been dropping.
Nationwide, the rate of kindergartners with complete records for the measles vaccine declined from around 95 percent before the pandemic to under 93 percent last year, according to the Centers for Disease Control and Prevention. Immunization rates against polio, whooping cough and chickenpox fell similarly.
Average rates remain high, but those national figures mask far more precipitous drops in some states, counties and school districts.
In those areas, falling vaccination rates are creating new pockets of students no longer protected by herd immunity, the range considered high enough to stop an outbreak. For a community, an outbreak can be extremely disruptive. For children, measles and other once-common childhood diseases can lead to hospitalization and life-threatening complications.
Immunization rates fell in most states early in the pandemic, and continued to fall in the years that followed.
States, not the federal government, create and enforce their own vaccine mandates, but the incoming Trump administration could encourage anti-vaccine sentiment and undermine state programs. The president-elect’s nominee for health secretary, Robert F. Kennedy Jr., has spread the false theory that vaccines cause autism, among other misinformation.
But immunization rates had been falling for years before Mr. Kennedy’s recent political rise.
There are now an estimated 280,000 kindergartners without documented vaccination against measles, an increase of some 100,000 children from before the pandemic.
“These pockets are just waiting for an introduction of measles,” said Dr. William Schaffner, an infectious disease specialist at Vanderbilt University Medical Center. “It’s trouble waiting to happen.”
Why rates are falling
As the pandemic strained trust in the country’s public health system, more families of kindergartners formally opted out of routine vaccines, citing medical, philosophical or religious reasons. Others simply didn’t submit proof of a complete vaccination series, for any number of reasons, falling into noncompliance.
The shifts in exemptions mostly fall along political lines. In states that supported Mr. Trump for president in November, the number of students with official exemptions have increased on average (rising everywhere but West Virginia). Exemption rates rose in a few states that supported Vice President Kamala Harris — including Oregon, New Jersey and Minnesota — but stayed relatively flat or fell in most.
The pattern for noncompliance looks different: The rate of children with no vaccination record shot up in both red and blue states.
Not all children with missing records are unvaccinated. Some are in the process of getting their shots, delayed because of the pandemic, and others just never submitted documentation. Schools are supposed to bar out-of-compliance students from attending, but whether they do varies from state to state and school to school.
Surveys reveal a new and deep partisan division on this issue. In 2019, 67 percent of Democrats and Democratic leaners told Gallup that childhood immunizations were “extremely important,” compared with 52 percent of their Republican counterparts. Five years later, the enthusiasm among the Democratic grouping had fallen slightly to 63 percent. For Republicans and G.O.P. leaners it had plunged to 26 percent.
Today, 31 percent of Republicans say “vaccines are more dangerous than the diseases they were designed to protect.” Just 5 percent of Democrats say the same.
“There seems to be a divide in terms of people’s feelings about science and skepticism towards the government,” said Dr. Natasha Bagdasarian, chief medical executive for Michigan. “I think some of those divisions are becoming apparent in vaccination rates.”
Lawmakers in numerous states have tried to roll back school vaccine mandates, but most changes have been minor: Louisiana required schools to pair any mandate notifications with information about exemption laws; Idaho allowed 18-year-old students to exempt themselves; and Montana stopped collecting data from schools on immunizations.
But there are a few places where state-level policy changes, or lack thereof, appear to have had a direct effect on rates.
In Mississippi, which had long held the country’s highest kindergarten measles vaccination rate, a federal judge ordered the state to allow religious objections; the state’s vaccination rate fell. In contrast, West Virginia’s governor vetoed a bill that would have loosened school vaccine policy; the state now has the highest rate.
Rates rose in Maine and Connecticut, two states that eliminated nonmedical exemptions during the pandemic. They also rose in Alabama, according to C.D.C. data, though the state declined to comment on why.
Vulnerable pockets
Epidemiologists say that when vaccination rates slip under 90 percent for measles, outbreaks become significantly harder to contain. At some point below that, spread becomes almost inevitable if measles is introduced.
There are thousands more schools with vaccination rates below 90 percent compared with just five years ago, according to a New York Times analysis of detailed data from 22 states.
Schools with falling rates can be found in red and blue states, in large urban districts and in small rural ones.
Measles vaccination rates dropped from 83 percent to 75 percent in Yavapai County in Arizona; from 93 percent to 78 percent in Pacific County on the coastline of Washington; from 97 percent to 93 percent in Union County, N.J., just outside New York City — places that span the political spectrum.
These numbers capture vaccination rates only for kindergartners, often partway through the school year, so they include students who may have finished their vaccine series later or will go on to finish it. And across the U.S., most students remain protected against childhood diseases.
But high rates nationally don’t help places no longer protected by herd immunity, as evidenced by recent outbreaks of childhood diseases. Measles and whooping cough cases both climbed last year; polio partly paralyzed a man in New York in 2022.
Growing anti-vaccine sentiment is only part of the public health challenge. In the Minneapolis public schools, completion rates for the measles, mumps and rubella vaccine among kindergartners dropped from around 90 percent to 75 percent. The district’s exemption rate barely moved; instead, far more students had incomplete vaccination records.
Few of those students’ families are strongly anti-vaccine, said Luisa Pessoa-Brandao, director of public health initiatives with the Minneapolis Health Department. Some are immigrants who moved into the district recently, missing either shots or records. Others missed regular doctor visits during the pandemic and got out of the habit of preventative care.
“I think we’re going to be catching up for a while,” Ms. Pessoa-Brandao said.
While vaccination rates were dropping in Minneapolis, they climbed in neighboring St. Paul Public Schools, from around 91.4 percent to around 93 percent, according to state data.
The district attributed the rise to strict new procedures started in 2021, including letters and phone calls to families in their native languages; more vaccines available on district grounds; and monthly compliance reports — an extra mile that not every district is able or willing to go.
There are still parents who opt out. But during a measles outbreak last year, a few changed their mind, said Rebecca Schmidt, the St. Paul district’s director of health and wellness.
“The fear of measles,” she said, “is sometimes greater than the ease” of getting an exemption.
Data for all 50 states
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