A maternal history of Alzheimer's disease appears to predispose individuals to the mind-robbing disease because their brains aren't using glucose efficiently, according to new findings presented at the Alzheimer's Association 2008 International Alzheimer's Disease Conference held in Chicago.
The new findings by a group led by Lisa Mosconi, Ph.D., research assistant professor of psychiatry at the Center for Brain Health at NYU Langone Medical Center, bolster a previous study published last year by the same group in the Proceedings of the National Academy of Sciences. That preliminary study of 49 people found reductions in glucose brain metabolism among individuals with a maternal history of the disease, but not among those with a paternal history or with neither parent affected.
The new findings extend the original observations to two years. Dr. Mosconi presented her findings at the Alzheimer's conference. "Our new study shows that subjects with a mother with Alzheimer's show similarities with Alzheimer's patients," says Dr. Mosconi. "They have metabolic reductions in the brain regions that are typically affected by AD, which worsen over time," she says.
In the latest study, the researchers studied glucose metabolism in the brain, using PET scans and a technique that labels glucose with a chemical tracer (FDG-PET) over a two-year period. Dr. Mosconi examined 66 cognitively normal individuals, from 50 to 82 years old. Twenty had mothers with the disease, and nine had fathers with Alzheimer's. The rest had no family history of the disease. Regions of the brain actively using glucose light up on the scans. Individuals with a maternal history of the disease had progressive metabolic reductions in glucose usage, and at a much faster rate, in areas of the brain affected by Alzheimer's disease than subjects with a paternal history or no parent with the disease.
These observations must be replicated, says Dr. Mosconi, and subjects need to be followed over longer periods of time to evaluate their risk for developing clinical symptoms. If the maternally transmitted reduced glucose metabolism is a risk factor for Alzheimer's, then it may be of value to search for potential mechanisms of disease in the interests of developing therapies to prevent or delay the onset, adds Mony de Leon, Ed.D., professor of psychiatry and director of the Center for Brain Health at NYU Langone Medical Center.
A family history of Alzheimer's is a known risk factor for Alzheimer's, which afflicts more than 5 million Americans and is the most common form of senile dementia. Individuals with an affected parent have a four- to ten-fold greater risk than those with no family history. The unique contribution of this study is to highlight that the maternal risk for AD in the offspring is potentially mediated through reduced brain metabolism, says Dr. de Leon.
It isn't known why people with a maternal history would be at greater risk, says Dr. Mosconi. Rare genetic mutations are responsible for the early-onset form of familial Alzheimer's, but people with a family history of late-onset disease (after age 55) don't carry any known genes. Dr. Mosconi is now investigating whether genetic material—the DNA carried in the mitochondria, the energy factories of cells—which is passed only from mothers to their offspring may play a role.
Dr. Mosconi's co-investigators on this study are: Rachel Mistur, Miroslaw Brys, Remigiusz Switalski, Lidia Glodzik, Elizabeth Pirraglia, Kenneth Rich, Wai Tsui, Susan De Santi, and Mony De Leon.
Materials provided by NYU Langone Medical Center / New York University School of Medicine. Note: Content may be edited for style and length.
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