Ceramides in Blood May Signal Alzheimer’s Disease Risk

High levels of a family of lipids called ceramides in the blood may be predictive of developing Alzheimer’s disease, a new study suggests.

Women with the highest levels of ceramides had a 10-fold higher risk of developing Alzheimer’s compared with those with the lowest levels, said Michelle M. Mielke, PhD, from the Mayo Clinic, Rochester, Minnesota.

“The study is small — that’s a limitation, and it was a preliminary study. However, given the small sample size, to have hazard ratios that are near 10 was quite striking and we didn’t expect to see that at all,” Dr. Mielke told Medscape Medical News.

“Pretty much any marker is not going to be associated with a 10-fold risk, so yes, this does need to be replicated in another study, but it suggests to us that plasma or blood ceramide levels are associated with an increased risk of Alzheimer’s disease,” she said.

Results of the preliminary study were published online July 18 in Neurology.

High Ceramide Levels

Previous studies have found links between high serum ceramide levels and memory impairment and hippocampal volume loss. In this study, Dr. Mielke and her group wanted to see whether blood levels of ceramides and sphingomyelins would be associated with increased risk of Alzheimer’s disease (AD).

Researchers used participants who were enrolled in the Women’s Health and Aging Study II, a longitudinal, population-based study of healthy women 70 to 80 years of age, living in Baltimore, Maryland. None had dementia at baseline.

Participants were followed for up to 6 visits over 9 years. Their blood was collected at baseline and at each subsequent visit.

Of 99 women, 27 (27.3%) developed incident dementia. Of these, 18 (66.7%) were diagnosed with probable Alzheimer’s disease.

The study found that higher baseline serum ceramides were associated with increased risk of Alzheimer’s disease. Higher levels of sphingomyelins were not linked to increased Alzheimer’s disease risk.

However, women in the middle tertile of serum ceramide levels had the highest risk for Alzheimer’s versus those in the lowest tertile, with an intermediate increased risk seen among those in the highest tertile.

“We think that this might indicate a threshold effect for the ceramides, so it may be that instead of high levels being a risk factor, low levels are protective. We haven’t quite figured that out, and further studies are needed to better determine this threshold effect,” Dr. Mielke said.

She added that she and her group currently have a study of more than 1000 people with some 4500 blood samples ongoing.

“We are just starting to get the data in,” she noted. “The thing with these lipids is that the assay methods are a bit more difficult than they are for some of the more common lipids, and so we are working on trying to develop more of a high throughput method, and one that can be used reliably across laboratories. That is one of the reasons why these tests haven’t been done in bigger population-based studies, and we are just starting to get into that route right now.”

The next goal is to examine what normal ceramide levels are and what factors affect them, she added.

Findings Noteworthy

Writing in an accompanying editorial, Valory Pavlik, PhD, of the Alzheimer’s Disease and Memory Disorders Center at Baylor College of Medicine, Houston, Texas, called the study findings “noteworthy.”

Identification of an accurate biomarker to predict Alzheimer’s disease, “which can be obtained with a minimum of cost and inconvenience to the individual, would greatly facilitate the transition of AD therapeutics research from the traditional model focused on treating established disease to a model focused on preventing or delaying disease onset,” Dr. Pavlik writes.

The study was funded by the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, and the Johns Hopkins Older Americans Independence Center. Drs. Mielke and Pavlik have disclosed no relevant financial relationships. (Fran Lowry)