Mental Health

New Evidence Alzheimer’s Disease Inherited From Mothers

March 4, 2011 — Mothers with Alzheimer’s may be more likely to pass the disease down to their children, a new study suggests.

The work is preliminary, but investigators identified twice as much gray matter volume reduction in disease-vulnerable areas of the brain in people with a maternal history of late-onset Alzheimer’s than those with a father with the disease or those with no family history.

“It is estimated that people who have first-degree relatives with Alzheimer’s disease are 4 to 10 times more likely to develop the disease themselves compared to people with no family history,” lead investigator Robyn Honea, DPhil, from the University of Kansas School of Medicine in Kansas City, said in a news release.

Allison Gandey

March 4, 2011 — Mothers with Alzheimer’s may be more likely to pass the disease down to their children, a new study suggests.

The work is preliminary, but investigators identified twice as much gray matter volume reduction in disease-vulnerable areas of the brain in people with a maternal history of late-onset Alzheimer’s than those with a father with the disease or those with no family history.

“It is estimated that people who have first-degree relatives with Alzheimer’s disease are 4 to 10 times more likely to develop the disease themselves compared to people with no family history,” lead investigator Robyn Honea, DPhil, from the University of Kansas School of Medicine in Kansas City, said in a news release.

“Using 3-D mapping methods, we were able to look at the different regions of the brain affected in people with maternal or paternal ties to Alzheimer’s disease,” Dr. Honea explained. “In people with a maternal family history of the disease, we found differences in the breakdown processes in specific areas of the brain that are also affected by Alzheimer’s disease leading to shrinkage.”

Asked by Medscape Medical News to comment, Debra Fleischman, PhD, from the Rush Alzheimer’s Disease Center in Chicago, Illinois, said, “Neurologists should know that a pattern of regional cortical thinning has been demonstrated in persons at risk for Alzheimer’s disease and that this pattern may be influenced by maternal family history.”

The results are published in the March 1 issue of Neurology.

Regional Cortical Thinning

There are several studies showing that individuals without dementia who have mothers with Alzheimer’s disease experience changes in memory performance, reductions in brain glucose metabolism in parietotemporal cortices and posterior cingulate, and increased β-amyloid load.

The researchers studied 53 dementia-free people 60 years and older. Of these, 11 reported having a mother with Alzheimer’s disease, 10 had a father with the disease, and 32 had no family history of dementia. Investigators administered magnetic resonance imaging and cognitive tests at baseline and then after 2 years.

They used a custom voxel-based morphometry processing stream to examine regional differences in atrophy between groups.

Investigators found that cognitively healthy people with a mother with Alzheimer’s had significantly increased whole-brain gray matter atrophy and cerebral spinal fluid expansion compared with the other groups.

Consistent with other studies.

The voxel-based analysis revealed these subjects also had significantly greater atrophy in the precuneus, parahippocampal, and hippocampus regions compared with people with fathers with Alzheimer’s disease or those with no family history, independent of APOE4 status, sex, and age.

They also analyzed APOE4-related atrophy and found those with the risk allele ε4 showed more regional atrophy in the frontal cortex compared with non-ε4 carriers.

“What we saw is consistent with other studies,” senior study author Jeffrey Burns, MD, from the University of Kansas, said during an interview. “We cannot yet extrapolate this to individuals in clinical practice. We will need larger studies for that.”

However, Dr. Burns said, “There seems to be something different in what people are inheriting from their mothers than their fathers. We expect this study will change some perceptions about familial history.”

The genetic basis for the transmission of Alzheimer’s disease is unknown. The investigators suggest mitochondrial DNA may play a role. “Given both its maternal transmission and evidence supporting a role for mitochondrial DNA abnormalities in Alzheimer’s disease,” they write.

Step Forward

Dr. Fleischman points out that although the study is limited by a small sample size, it represents another step forward in identifying a unique imaging endotype for people at risk for Alzheimer’s disease.

“The next step would be to directly examine the association of regional cortical thinning with amyloid burden in maternal family history, which this study does not do. It will also be important to examine this pattern of cortical thinning in maternal family history with other, potentially treatable, risk factors for Alzheimer’s disease.”

Dr. Fleischman points out, “Other work has suggested that regional cortical thinning, particularly in precuneus, is associated with systemic inflammation in older persons without dementia. It would be of interest to examine whether those persons with maternal family history and regional cortical thinning are more likely to have systemic inflammation and/or neuroinflammation.”

The investigators say they hope that understanding how the disease may be inherited could lead to better prevention and treatment strategies.

This study was funded by the National Institute on Aging and the National Institute of Neurological Disorders and Stroke. Dr. Burns has received funding from Pfizer, Novartis, Medacorp Consulting, Johnson County Clinical Trials, PRA International, Elan, Janssen, Wyeth, Danone, and the Dana Foundation. He has served as an expert witness in legal proceedings regarding competency. Dr. Honea and Dr. Fleischman have disclosed no relevant financial relationships.

Allison Gandey is a journalist for Medscape. She is the former science affairs analyst for the Canadian Medical Association Journal. Allison, who has a master of journalism specializing in science from Carleton University, has edited a variety of medical association publications and has worked in radio and television. She can be contacted at [email protected]

Neurology. 2011;76:822-829.

Medscape Medical News © 2011 WebMD, LLC

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