APOE4 may also detect brain aging

A Duke University researcher has found signs of accelerated aging in the brains of healthy people who have a well-known genetic marker for Alzheimer’s disease (AD). Are they on their way to Alzheimer’s, or is this something different?

His unpublished results will help to resolve the question – but at the moment another researcher in the field is dubious that he has truly found a new phenomenon.

P. Murali Doraiswamy reported the newfound link between brain aging and the APOE4 allele, which is well known to be associated with Alzheimer’s disease, this week at the American Association of Geriatric Psychiatry. His team has used a novel application of an established technique, magnetic resonance spectroscopy (MRS), to measure a surrogate marker for brain aging, N-acetylspartate (NAA), in the frontal lobes of 165 healthy people aged 55 to 85, and then related these levels to whether or not they carry APOE4.

Doraiswamy and his colleagues used MRS, an adaptation of magnetic resonance imaging (MRI) “because it’s non-invasive, and because we can get metabolic information, just as if I had cut out a piece of tissue, and we can do this serially [over time],” said Cecil Charles from Duke’s Images Analyses Laboratories.

NAA levels in the frontal cortex declined “mildly” with age among all the participants in the study (R=-0.28, p<0.05); according to Doraiswamy many prior findings in the field suggest that everyone suffers from some age-related decline in frontal lobe nerve cell function. However, “the average loss of NAA across the age span was nearly threefold higher in people with the APOE4 gene than in those who were not carriers,” he said. (R=-0.45, p<0.001). Further, the APOE4 group was younger. If anything, he said, if the phenomenon could be explained by age alone, that group should have shown it to a lesser degree.

Previous studies have reported exaggerated changes in NAA levels in patients with full-blown Alzheimer’s disease who carry APOE4.

“To the best of my knowledge, this is the first report in which this technique has been employed to study a cognitively intact elderly population,” said New York University geriatric psychiatrist Nunzio Pomara, who chaired the session in which Doraiswamy presented his findings.

But Rob Friedland is not convinced that the study participants were all healthy. “The researchers found changes in the brains of those carrying APOE4, but this is probably because some of these individuals had very early stages of Alzheimer’s disease, and not as a result of brain aging,” the Case Western Reserve University researcher said in an interview, adding that Alzheimer’s and brain aging are not necessarily the same.

Friedland also disagreed with Doraiswamy’s premise that the frontal cortex is “the place where the earliest and most consistent effects of aging occur in the brain.” Aging effects occur in the temporal lobe as well, particularly in the hippocampus, he said. “They are testing part of the changes, but not all of them.”

But Doraiswamy has noted that his study looked at the frontal lobe intentionally, because preclinical AD-related changes “are more likely to occur in the temporal lobe,” he told BioMedNet News. “It’s still possible that our findings represent not just accelerated normal aging in this group, but also an increased rate of preclinical Alzheimer’s-type changes,” he said.

Doraiswamy adds that he intends to look at how different agerelated changes are between those patients who have both the APOE4 allele and a family history of AD, to those who have neither. He will also follow his subjects to see if those with the lowest NAA levels go on to develop Alzheimer’s.

• Alzheimer’s amyloid proponents pinpoint precursors (0)