In mid-November New York magazine ran a cover story on a group of 540 Ashkenazi Jews who, as the headline trumpets, carry "DNA You Wouldn't Believe." This group of happy oldsters, all of them over 95, might hold the key to extreme longevity, the article suggests. There is the 105-year-old stockbroker who still goes to work everyday and a peripatetic 109-year-old woman.
The article—"What Do a Bunch of Old Jews Know about Living Forever?"—highlights research from the Albert Einstein College of Medicine in the Bronx that points to several genes that might help explain the secret of a Methuselah-like existence. One, in particular, stands out, the Einstein researchers assert. The oldest of the old who bear a certain version of the cholesteryl ester transfer protein gene, (CETP I405V) end up with lower levels of the CETP protein but higher levels of the "good" cholesterol, and larger particles of these high-density lipoproteins (HDLs). The carriers of two copies of this gene variant—one from ma, one from pa— appear to have a lower risk of dementia, failing memories and heart disease.
There is a problem with this halcyon picture. A few weeks after the New York article hit the presses, a report by researchers from Rush University Medical Center in Chicago in a respected journal, Aging Cell, identified the CETP variant as a gene that may increase the risk of Alzheimer's. The same version of the same gene: in one study it slows dementia, in the other it promotes cognitive decline.
What is going on here? Two groups of well-regarded researchers come to the exact opposite conclusion. Welcome to the wild-and-wooly world of gene-association studies that attempt to tie DNA to disease. Unless the link between a gene and a disease or phenotype is a very strong one, researchers who try to follow up on initial studies often get different results the second or third time around.
In this instance, the researchers at Rush had decided to investigate this gene after reading a January study published in JAMA The Journal of the American Medical Association by the Einstein investigators. The JAMA article found that the CETP variant protected a diverse group of older people, aged 70 and older, not just the Ashkenazim, against failing memory and dementia. The JAMA study, though, extended earlier work by the Einstein researchers that showed better cognition and general health in the Ashkenazi super old that carry the gene.
The Rush team, which oversees two well-known longitudinal studies on aging and dementia, decided to see whether they could replicate the JAMA findings. Their analysis of 1,384 participants from the two studies found that the CETP variant was associated with a faster rate of cognitive decline and an increased risk of Alzheimer's. The Chicago researchers then did something that the Einstein team hadn't. They went to pathology information collected on the brains of 590 of the deceased study participants. They found there that those with the relevant CETP variant had a greater density of the plaques characteristic of Alzheimer's than others who didn't.
So who is right? Maybe no one at all. A leader of the Rush team points out the possibility that both results may be due to chance "They got an effect, they reported it; we got an opposite effect, we reported it," said David Bennett, a professor of neurological sciences at Rush and one of the co-authors on the paper. "Maybe the truth is in the middle, which is no effect."