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Untangling Minds

click for larger imageTreatments for Alzheimer’s disease today are modest in effect, merely slowing the progression of symptoms. That’s partly because scientists until recently had identified only four genes that contribute to the disease. Many more genes are believed to be involved, setting off numerous biological malfunctions that together create the sticky, fibrous plaque that destroys the diseased brain.

Columbia researchers led by Richard Mayeux ’91PH have discovered another piece of that puzzle. They recently concluded that a fifth gene, called SORL1, is associated with Alzheimer’s. The gene is only the second identified as contributing to late-onset Alzheimer’s, the most common form of the disease, affecting people over the age of 65 and accounting for 90 percent of all cases. The first gene, ApoE4, was linked to late-onset Alzheimer’s in 1993.

Mayeux, codirector of Columbia’s Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, published the findings in the February issue of Nature Genetics in collaboration with scientists at the University of Toronto, Boston University, and 12 other institutions. The federally funded researchers examined the DNA of more than 6000 people, including several hundred Dominicans living in the Washington Heights neighborhood of Manhattan.

They examined members of six ethnic groups in several cities and found that variants in the gene SORL1 are more common in people with late-onset Alzheimer’s than in healthy individuals of the same age. The finding held true across four ethnic groups: Caribbean-Hispanic, Northern European, African-American, and Israeli-Arab.

The researchers aren’t sure exactly where the relevant mutations are on SORL1. That’s the next stage of their research, and it’s a tricky challenge, because SORL1 is thought to have upward of 500 common variations, an unusually large number. The scientists have examined about 30 so far and haven’t yet found a single mutation that is clearly linked to the disease among any of the ethnic populations.

“The causal mutations we’re looking for are probably quite subtle, because if they were major mutations they would cause disease earlier in life,” says Mayeux, the Gertrude H. Sergievsky Professor of Neurology, Psychiatry, and Epidemiology. “That SORL1 is involved in late-onset Alzheimer’s would indicate that it functions pretty normally until old age, and then for some reason it peters out.”

What exactly is SORL1’s role in causing the disease? Scientists have known for a few years that SORL1 produces a protein, also called SORL1, which acts as a sort of intercellular traffic cop, directing other proteins and molecules down pathways where they’ll metabolize properly. A key molecule that’s directed by the protein SORL1 is amyloid precursor protein (APP), which turns into the obstructive plaque found in diseased brains, most Alzheimer’s experts believe.

Mayeux says that mutations in the gene SORL1 reduce the amount of protein it produces, which in turn allows APP to stray into cellular regions where it takes on its toxic form. Physiologic research supports that working hypothesis: The scientists last year found that levels of the protein SORL1 are very low in individuals with late-onset Alzheimer’s.

The scientists hope that by identifying exactly which SORL1 mutations are at work in this process, they’ll eventually help develop new treatments, as well as genetic screening tools to identify susceptibility to Alzheimer’s. Researchers say it’s too early to determine what percentage of Alzheimer’s cases the gene SORL1 might help explain; the gene ApoE4 is implicated in about 20 percent of late-onset Alzheimer’s cases, and SORL1 is thought to be involved in causing a smaller percentage.

“Alzheimer’s vaccines that get rid of some proteins in the body have been developed, but they cause other illnesses, like encephalitis, and so they’ve never become available,” says Mayeux. “If we can develop a genetic test that determines, without a doubt, that some people will develop Alzheimer’s, then they can decide whether to take those risks.”

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A nose for the truth

click for larger imageA mysterious stench that wafted over parts of New York City and New Jersey on the morning of January 8, briefly hospitalizing 19 people and shutting down subways and schools, generated lots of explanatory theories. A natural gas leak was ruled out within a couple of hours, and suspicions turned to air pollution and sewage fumes. Some New York City politicians pinched their noses and blamed New Jersey chemical plants, prompting defensiveness across the Hudson. “I think New York officials should stop pointing fingers and work with the New Jersey DEP if they have a theory,” said Elaine Makatura, a spokesperson for the New Jersey Department of Environmental Protection. “We’re not too sure the smell didn’t come from New York,” added Anthony Iacono, town administrator for Secaucus, New Jersey.

Everybody seemed to agree that the overpowering odor was reminiscent of rotten eggs, and nothing like the thick smell of maple syrup that blanketed Manhattan on separate occasions in the autumns of 2003 and 2005. That olfactory mystery is still unsolved, as this one might have remained, too, if not for the investigative efforts of four Columbia environmental scientists and one from Barnard. They combined their knowledge of marine biology, air and water pollution, and weather patterns to study the incident on their own time for several days afterward. They concluded that the smell emanated from bacteria in salt marshes along the shores of Staten Island and in Jamaica Bay, nestled between the southern shores of Queens and Brooklyn. The scientists described their findings in a January 21 New York Times op-ed, and as yet, the authors say, no one has challenged them.

The New York City shoreline is rich with microorganisms feasting upon organic matter, according to the scientists, because treated sewage gets deposited there. Sulfur-based gases like hydrogen sulfide get released into the air when saltwater washes over the sediment, causing a chemical reaction. Western winds blowing down from the Poconos typically push the smell out to sea. This happens more or less continuously in warm weather, but not when freezing temperatures stop the decomposition.

But a couple things happened differently leading up to the Monday morning in question. First, a stretch of unseasonably warm temperatures thawed the ground, so “a lot of sediment was built up” and waiting to decay, says geochemist Wade McGillis, one of the authors of the Times op-ed and a Columbia associate professor. In addition, a weather phenomenon called an atmospheric inversion occurred early that morning. That means that high- and low-pressure weather systems collided and warm air settled above the cold air, trapping a pocket of cool air near the ground. To make matters worse, winds in the metropolitan area nearly disappeared for a few hours. As a result, a low-lying bubble of stink strayed inland, where it parked itself until midday, when winds picked up again and dispersed it.

The scientists figured all this out by examining data from Columbia air sensors atop buildings across Manhattan, and information from the National Weather Service and the U.S. Air Force. They also calculated how much sulfur-based gas the shoreline sediment could give off, and the numbers added up.

“Our explanation highlights the consequences of exposing water to sewage, fertilizer, chemicals, or other pollutants,” they wrote in the Times. “Of course, these consequences go beyond odor — they kill marsh vegetation, degrade the wider marine habitat, and make it unsafe to swim or fish.

“Yes, water quality in the New York area has become better in recent decades,” they continued. “But there is still much room for improvement.”

The other op-ed authors were Brian Mailloux, an assistant professor of environmental sciences at Barnard, and Greg O’Mullan, Ray Sambrotto, and Philip Orton, who like McGillis are scientists at the Lamont-Doherty Earth Observatory.

Katrina’s grim legacy

Thousands of Mississippi families, their lives uprooted by Hurricane Katrina, face worsening mental and physical health problems as a result of the ordeal, Columbia researchers say.

A new report finds that Mississippi children displaced by the disaster show signs of depression, anxiety, and behavioral problems, with many missing substantial amounts of school. Their parents are suffering from similar problems, ranging from depression and hypertension to posttraumatic stress syndrome. In addition, the region’s poorest families have slid further down the economic ladder, being unable to find jobs to replace the ones they lost after the August 2005 hurricane.

The researchers, led by David Abramson of the Mailman School of Public Health’s National Center for Disaster Preparedness, studied Mississippi residents among 576 randomly selected households displaced or otherwise seriously affected by Katrina. Their findings are based on interviews conducted last August, many in Federal Emergency Management Agency trailer parks. The study follows up on a similar report the researchers completed six months earlier. Emotional and behavioral issues among children, and mental health problems among adults, became more prevalent across the two studies.

Since Katrina, according to the researchers, there has been a fourfold increase in diagnosis of depression or anxiety among displaced children and three times as many children are without health insurance. More than 60 percent of displaced parents or caregivers suffer from clinical anxiety, depression, and posttraumatic stress disorder. Meanwhile, rates of hypertension among adults increased 35 percent since the hurricane.

The working poor suffered the worst economic impact. More than half of the households with an annual income below $10,000 lost their jobs after the hurricane, the new study finds, compared to 15 percent of households with annual income above $20,000.

The report recommends that the government institute job-training, skill-building, and homeownership programs. But “for the poorest and most vulnerable populations, there is no [aid] pipeline in sight,” the researchers write. “They are the least likely to be homeowners, and the individual assistance they did receive — such as temporary housing or rental vouchers — may soon be coming to an end.”

Learning to truss

click for larger imageAs part of the architecture school’s 125th anniversary celebration last semester, teams of graduate students created two seven-foot-high, curvy metal structures in Low Library to demonstrate a novel building approach.

Using so-called “space truss” technology developed at the architecture school’s Avery Digital Fabrication Lab, the students designed three-dimensional forms on computers and then cut to specification stainless steel components with high-powered, laser-guided water jets in the lab. They manually assembled the pieces following instructions generated by the computer.

The building system they used, Trusset, was developed two years ago by adjunct faculty members Cory Clarke ’97GSAPP and Philip Anzalone ’97GSAPP, the lab’s technical director. The patented technology converts any shape into a web of nodes and straight lines and guides the manufacture and assemblage of the network. The metal latticework can be covered with panels of aluminum or other materials to create frames for temporary structures or the permanent backbone of wall partitions or large structures such as pavilions or auditoriums. Similar building systems, Clarke and Anzalone say, are less automated and more expensive.

Students who work with the technology every day in Anzalone’s lab, meanwhile, get hands-on experience with computer-assisted fabrication tools used commonly on architecture projects. “Making curved designs is always complex, and it finds its way into almost any advanced architectural job,” says Anzalone. “The students also experience moving from design to the building process.”


Alcohol abuse rises on college campuses

Drinking on college campuses is practically accepted as a rite of passage in our society. But a major Columbia study provides a reality check: U.S. college students are abusing alcohol with increasing intensity and facing serious consequences as evidenced by physical injuries.

The four-year study, conducted by Columbia’s National Center on Addiction and Substance Abuse (CASA), shows that between 1993 and 2005 the proportion of students in this country who drank irresponsibly remained flat at about 40 percent. But the proportion of students who say they binge drank frequently shot up 16 percent, as did the proportion of those who say they drank more than 10 times a month, up 25 percent, and those who drank to get drunk, up 21 percent.

The proportion of college students who were injured as a result of their own drinking increased 38 percent from 1993 to 2001. The researchers also note that in 2001 about 97,000 students were victims of alcohol-related rape or sexual assaults.

The authors, led by CASA chair and president Joseph A. Califano, Jr., report that nearly 38 percent of college administrators say the most significant barrier to preventing student alcohol and drug abuse is public perception that such behavior is a normal part of the college experience. They also found that 37 percent of college students who abuse substances don’t seek help because they fear social stigmatization.

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