We conduct research on earthquakes and tsunamis at the Alaska Earthquake Center, and one of us serves as Alaska state seismologist. In a new study with colleagues, we detail how that landslide sent water and debris 1,580 feet (481 meters) up the other side of the fjord – higher than the top floor of the Taipei 101 skyscraper – and then continued down Tracy Arm. The force of the water stripped the fjord’s walls down to bare rock.

It was just after 5 o’clock in the morning on a dreary day, and fortunately, no ships were nearby. In the months after, some cruise lines started avoiding Tracy Arm. However, the conditions that led to this event are not at all unique to this fjord.

Landslides are common in the coastal mountains of Alaska where rapid uplift, caused by tectonic forces and long-term ice loss, converges with the erosive forces of precipitation and moving glaciers. But a curious pattern has emerged in recent years: Multiple major landslides have occurred precisely at the terminus of a retreating glacier.

Though the mechanics are still poorly understood, these mountains appear to become unstable when the ice disappears. When the landslide hits the water, the momentum of millions of tons of rock is transferred into tsunami waves.

This same phenomenon is playing out from Alaska to Greenland and Norway, sometimes with deadly consequences. Across the Arctic, countries are trying to come to terms with this growing hazard. The options are not attractive: avoid vast swaths of coastline, or live with a poorly understood risk. We believe there is an obvious role for alert systems, but only if scientists have a better understanding of where and when landslides are likely to occur.

Signs that a landslide might be coming

The Tracy Arm landslide is a powerful example.

The landslide occurred in August, when warm ocean waters and heavier precipitation favor both glacier retreat and slope failure. The glacier below the landslide area had experienced rapid calving – large chunks of ice breaking off and falling into the water – and it had retreated more than a third of a mile in the two months prior. Heavy rain had been falling. Rain enters fractures in the mountain and pushes them closer to failure by increasing the water pressure in cracks.

Most provocative are the thousands of small seismic tremors that emanated from the area of the slide in the days prior to the mountainside collapsing.

We believe that this combination of signs would have been sufficient to issue progressive alerts to any ships in the vicinity and homes and businesses that could have been harmed by a tsunami at least a day prior to the failure – had a monitoring program existed.

Escalating alerts are used for everything from terrorism and nuclear plant safety to avalanches and volcanic unrest. They don’t remove the risk, but they do make it easier for people to safely coexist with hazards.

For example, though people are still killed in avalanches, alert systems have played an essential role in making winter backcountry travel safer for more people. The collapse at Tracy Arm demonstrates what could be possible for landslides.

What an alert system could look like

We believe that the combination of weather and rapid glacier retreat in early August 2025 was likely sufficient to issue an alert notifying people that the hazard may be temporarily elevated in a general area. On a yellow-orange-red scale, this would be a yellow alert.

In the hours prior to the landslide, the exponential increase in seismic events and telltale transition to what is known as seismic tremor – a continuous “hum” of seismic energy – were sufficient to communicate a time-sensitive warning for a specific region.

These observations, recorded as a byproduct of regional earthquake monitoring, warranted an “orange” alert noting immediate concern. The signs were arguably sufficient to recommend keeping boats and ships out of the fjord.

Our research over the past few years has demonstrated that once a large landslide has started, it is possible to detect and measure the event within a couple of minutes. In this amount of time, seismic waves in the surrounding area can indicate the rough size of the landslide and whether it occurred near open water.

A monitoring program that could quickly communicate this would be able to issue a red alert, signaling an event in progress.

The National Oceanic and Atmospheric Administration’s tsunami warning program has spent decades fine-tuning rapid message dissemination. A warning system would have offered little help for ships in the immediate vicinity, but it could have provided perhaps 10 minutes of warning for those who rode out the harrowing tsunami farther away.

There is no landslide monitoring system operating yet at this scale in the U.S. Building one will require cooperation across state and federal agencies, and strengthened monitoring and communication networks. Even then, it will not be fail-proof.

Understanding risk, not removing it

Alert systems do not remove the risk entirely, but they are a better option than no warning at all. Over time, they also build awareness as communities and visitors get used to thinking about these hazards.

Many of the most alluring places on Earth come with significant hazards. Arctic fjords are among them. The same processes that create this hazard – glacier retreat, steep terrain, dynamic geology – are also what make these landscapes so compelling. The mix of glaciers, ice-choked waters and steep mountains is exactly what draws people to these places. People will continue to visit and experience them.

The question is not whether these places should be avoided altogether, but how to help people make more informed decisions. We believe that stronger geophysical and meteorological monitoring, coupled with new research and communication channels, is the first step.

On Aug. 9, visitors unknowingly passed through a landscape on the cusp of failure. An alert system might have given tour companies and people in the area the information they needed to make more informed choices and avoid being caught by surprise.

Now, researchers at Columbia University have uncovered a biological mechanism that could help explain this remarkable resistance. Their findings point to a rare genetic mutation that protects the brain’s blood vessels from damage, potentially opening a new path toward Alzheimer’s treatments.

The discovery builds on research the team published two years ago involving APOE ε4, a gene variant strongly associated with Alzheimer’s risk. The scientists found that some people carrying APOE ε4 also possess a rare protective mutation in the fibronectin (FN1) gene.

Fibronectin is a protein that helps support the structure of tissues. However, in people with APOE ε4, excessive amounts can accumulate around blood vessels in the brain, potentially compromising a critical protective system known as the blood-brain barrier. The rare FN1 mutation appears to limit this buildup and the damage associated with it.

That earlier discovery suggested an intriguing possibility: What if scientists could develop a treatment that recreates the protection provided by this rare mutation?

A new study published in Nature Aging brings that possibility closer by identifying how excess fibronectin damages the brain’s protective barrier and revealing potential ways to interrupt the process.

“This new study takes us from a genetic clue to a disease mechanism,” says Caghan Kizil, the study’s corresponding author and professor of neurological sciences in the Department of Neurology and the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University Vagelos College of Physicians and Surgeons.

“We knew that changes in fibronectin could protect against Alzheimer’s, but we didn’t know why excess fibronectin was harmful in the first place. This study gives us that detailed mechanism — and with it, ideas for how to reproduce that natural protection.”

How an Alzheimer’s Risk Gene Weakens the Blood-Brain Barrier

The blood-brain barrier serves as a protective boundary between the bloodstream and the brain. Made up of tightly connected cells surrounding the brain’s blood vessels, it carefully regulates which substances can enter brain tissue while helping maintain conditions necessary for removing potentially harmful waste.

When this barrier becomes damaged or excessively permeable, substances that would normally be kept out can enter the brain more easily. Such disruptions may contribute to inflammation and other processes involved in neurological diseases, including Alzheimer’s.

To investigate the role of fibronectin, the Columbia team combined several advanced research approaches. They examined human brain tissue and cerebrospinal fluid, the clear liquid surrounding the brain and spinal cord, using genetic and epigenetic analyses to explore changes in DNA and gene activity.

Their investigation also included single-cell sequencing, which reveals the activity of individual cells, and spatial imaging to examine where biological changes occur within tissues. Additional experiments involved human stem-cell models, three-dimensional cultures of blood vessels, and studies in zebrafish and mice.

Despite the variety of methods, the findings consistently pointed to the same mechanism: APOE ε4 promotes the production and accumulation of fibronectin around the brain’s blood vessels.

In mice engineered to carry human APOE ε4, researchers measured nearly twice as much fibronectin in the brain as in mice carrying APOE ε3, another common version of the gene. The greater accumulation was accompanied by evidence that the blood-brain barrier had become leaky.

Scientists Discover How Fibronectin Causes Brain Damage

One experiment provided especially important evidence that fibronectin does more than simply accumulate in damaged blood vessels.

The researchers increased human fibronectin specifically in astrocytes, specialized support cells that help maintain the blood-brain barrier and keep the brain functioning properly.

Increasing fibronectin in these cells was enough to disrupt the barrier, allowing it to become more permeable. Conversely, reducing fibronectin improved the barrier’s ability to function normally.

These results provided experimental evidence that excess fibronectin can directly contribute to blood-brain barrier damage rather than merely appearing alongside it.

“The animal experiments allowed us to move beyond association,” says co-first author Prabesh Bhattarai, an associate research scientist in the Kizil lab. “When we increased fibronectin in astroglia, the barrier became permeable. When we reduced fibronectin, barrier function improved.”

The team then investigated the molecular events responsible for the damage.

They found that excessive fibronectin interferes with communication between cells by activating abnormal signals through integrins, proteins that help cells sense and respond to their surroundings, and an enzyme known as focal adhesion kinase.

These abnormal signals disrupt a network of growth factors called VEGF, HBEGF, and IGF1. Although growth factors are often associated with cell development and repair, these particular signaling molecules also help astrocytes and blood vessel cells coordinate their activities to maintain a healthy blood-brain barrier.

When their communication becomes disrupted, the barrier can lose its integrity, potentially leaving brain tissue more vulnerable to damage.

“Single-cell analysis allowed us to examine this pathway in the different cells that maintain the brain’s blood vessels,” says co-first author Elanur Yilmaz, an associate research scientist in the Kizil lab. “We observed the same biological pattern across experimental models and human Alzheimer’s tissue, making the mechanism especially compelling.”

Evidence From Human Brains Strengthens the Alzheimer’s Connection

Importantly, the researchers found signs of similar biological disturbances in human samples, suggesting that the process identified in laboratory experiments may also contribute to Alzheimer’s disease in people carrying APOE ε4.

Analyses of brain tissue and cerebrospinal fluid showed that elevated fibronectin levels were associated with inflammation in astrocytes.

Genetic and gene-regulation analyses also connected FN1 to blood vessel disease and changes involving VEGFA, a growth factor that plays an important role in maintaining healthy brain blood vessels.

Together, these findings provide multiple lines of evidence linking excess fibronectin to the vascular damage associated with APOE ε4.

“The convergence of these independent human datasets strengthens the case that fibronectin is part of the APOE ε4-related vascular disease process,” says Badri Vardarajan, associate professor of neurological science in the Department of Neurology, Gertrude H. Sergievsky Center, and Taub Institute, who collaborated on this discovery of the FN1 mutation.

A Rare Genetic Defense Could Inspire New Alzheimer’s Treatments

The potential implications are significant because APOE ε4 is the strongest common genetic risk factor for Alzheimer’s disease. Approximately one in five people carries at least one copy of this gene variant.

Although carrying APOE ε4 does not guarantee that someone will develop Alzheimer’s, it increases their likelihood of developing the disease. Understanding why certain carriers remain unaffected could reveal new opportunities for prevention and treatment.

The latest findings suggest several possible approaches.

One strategy would be to prevent harmful amounts of fibronectin from accumulating around the brain’s blood vessels. Another would involve blocking the abnormal cellular signals triggered by excess fibronectin. A third possibility would be to restore the growth factor signaling that allows astrocytes and blood vessel cells to maintain the blood-brain barrier.

Researchers are already investigating these possibilities through laboratory experiments.

However, translating the discovery into a treatment will require considerable care. Fibronectin performs essential functions throughout the body, including supporting tissue structure and helping damaged tissues heal. Any future therapy would therefore need to target its harmful accumulation or effects without disrupting these beneficial activities.

By identifying the molecular mechanisms involved, scientists now have a more precise framework for designing such treatments. The findings may also help researchers determine when interventions would be most effective and how to measure whether they are successfully protecting the brain.

“By showing how fibronectin contributes to early vascular damage, this study gives us new therapeutic targets and potential ways to measure whether treatments are working,” says Richard Mayeux, chair of the Department of Neurology and a collaborator on the project. “Clinically, it connects a major genetic risk factor for Alzheimer’s to an early disease process that may be possible to modify.”

Although these potential therapies remain experimental, the discovery offers a promising new direction in Alzheimer’s research. Rather than focusing only on the damage that develops as the disease progresses, scientists may eventually be able to reproduce a natural genetic defense that helps protect vulnerable brains before significant damage occurs.

The researchers tracked almost 300 older adults with early brain signs of Alzheimer’s for nine to 11 years using pedometers. They found that physical activity didn’t reduce the toxic amyloid plaques that most Alzheimer’s treatments now target.

Instead, in people who already had these plaques, physical activity reduced the accumulation of misfolded tau proteins in specific brain areas. These proteins appear later in Alzheimer’s disease and are more closely linked to cognitive and functional decline. These signs of dementia were reduced by almost half in more active participants.

Benefits appeared at just 3,000 steps – roughly half an hour of walking at a moderate pace. The optimal range was 5,000 to 7,500 steps daily, after which the effect plateaued. More steps didn’t necessarily mean greater protection, which suggests a realistic target for older, sedentary people, rather than the often-cited 10,000 steps.

The study had limitations, however. It involved a fairly small group of mostly white, well-educated people in the US, and it didn’t take other lifestyle or health factors into account. Also, there may be other protective mechanisms of walking at play. But it does support other research suggesting that being physically active may lower the risk of dementia.

A UK study of 1,139 people over 50 found that those who were moderately to vigorously active had a 34-50% reduction in dementia risk when followed over eight to ten years. Among those who developed dementia, staying active reduced their memory decline, particularly in older women.

A larger 2022 UK study tracked 78,430 people for seven years using wrist accelerometers. It found a 25% reduction in dementia risk with just 3,800 steps daily, rising to 50% at 9,800 steps.

However, people who walked more also had better cardiovascular health – lower cholesterol, better sleep and blood pressure and reduced diabetes risk. Since these heart and stroke risk factors also increase dementia risk, the picture is complex.

Healthy habits often go together. People who exercise are more likely to eat well, not smoke, look after their heart health and have fewer financial stresses. This makes it hard to know which factor is having the biggest effect. The researchers tried to account for this, but because these habits are so closely linked, it’s difficult to say that exercise alone is responsible.

However, there is a strong case for this as there are multiple ways exercise might support the brain: improving cardiovascular health, increasing blood flow and boosting chemicals that promote brain-cell connections.

One such substance is irisin, a hormone produced by muscles that acts on almost all faulty brain mechanisms associated with Alzheimer’s, including inflammation. This and other chemicals, such as BDNF, associated with exercise, provide plausible biological pathways for how physical activity might directly influence brain health beyond its cardiovascular benefits.

But the relationship might work in reverse, too. People may become less active because of early Alzheimer’s symptoms. Those with hearing problems, for instance – itself a dementia risk factor – often report barriers that make them stop being active before other dementia symptoms appear.

Vicious circle

Reduced activity then accelerates memory decline. This creates a vicious circle. Early disease symptoms – such as not hearing – can affect self-esteem and reduce engagement in physical activity, which in turn worsens cognitive decline.

Brisk walking might be particularly beneficial. A small trial of 15 people with mild to moderate Alzheimer’s who did Nordic walking (an enhanced walking technique that uses poles to work your upper body as well as your legs) maintained brain function over 24 weeks, with some functions even improving.

The 15 who received only standard care showed decline or no improvement. Though small, the trial suggests that even people already diagnosed with Alzheimer’s might benefit from increased physical activity, including brisk walking.

Getting outside, particularly in nature, may be especially beneficial for preventing dementia – possibly because it improves mood and sleep while reducing isolation – all dementia risk factors. The combination of physical movement, natural light exposure and social interaction when walking outdoors may create multiple protective effects that complement each other.

The challenge now is helping people overcome barriers to outdoor activity, such as safety concerns, fear of falling, or simply preferring the comfort of the sofa – particularly during wetter, colder months. But the evidence suggests that even a few minutes of walking could make a difference, and that modest, achievable targets – a half-hour stroll rather than a marathon training regime – may offer substantial protection against cognitive decline.