Maternal link to Alzheimer's disease

People who have a mother with Alzheimer's disease appear to be at higher risk for getting the disease than those individuals whose fathers are afflicted, according to a new study by NYU School of Medicine researchers.

The study, published in online in the Proceedings of the National Academy of Sciences, is the first to compare brain metabolism among cognitively normal people who have a father, a mother, or no relatives with Alzheimer's disease.

It found that only individuals with an affected mother have reduced brain metabolism in the same brain regions as Alzheimer's patients.

Over the last two decades a number of studies have shown that people with the disease have significant reductions in brain energy metabolism in certain regions of the brain. In some recent research studies these reductions are evident in healthy people years before symptoms of dementia emerge.

It not yet known why people with a family history are more susceptible to the disease, nor why individuals with a history of the disease on their mother's side are at increased risk for Alzheimer's.

The observation must be replicated in larger studies before it could be of use in the clinic to perhaps identify people who may be more vulnerable to the disease, the study's first author, Assistant Professor Lisa Mosconi of the NYU School of Medicine, said.

Mosconi speculates that genes that are maternally inherited might alter brain metabolism.

The new study involved 49 cognitively normal individuals, from 50 to 80 years old, who underwent a battery of neuropsychological and clinical tests, and PET (positron emission tomography) scans of their brains using a technique that labels glucose-the brain's fuel-with a special chemical tracer.

Sixteen subjects had a mother with the disease, and eight had a father with Alzheimer's. The remaining subjects didn't have a family history of the disease.

People with a maternal history of the disease had the largest reductions in glucose metabolism in several areas of the brain, including the medial temporal lobes and the posterior cingulate cortex, two brain regions involved with memory storage and retrieval. Brain energy metabolism was reduced by 25 per cent in the posterior cingulate cortex in this group

There weren't any reductions in brain energy metabolism in the people without a family history and in those with a father who had the disease. The effects in glucose metabolism among subjects with a maternal history remained significant after accounting for possible risk factors for Alzheimer's, including age, gender, education, Apolipoprotein E genotype, and subjective memory complaints.

"This is a preliminary study and the results have to be replicated," Mosconi said.

"What we need even more is to follow subjects over time until they develop clinical symptoms, and we really need to assess whether the metabolic reductions predict and correlate with disease progression.

"Energy metabolism hasn't been a major focus of research in Alzheimer's, so we hope that this study will stimulate further discussion on brain activity and disease risk, which could also be important for planning targeted therapeutic interventions."

Source: New York University Medical Center and School of Medicine