"Disruption of metabolic function is a recognized feature of late onset Alzheimer's disease," says Mark Mapstone. (Credit: Getty Images )

Amyloid build-up isn’t the only Alzheimer’s risk factor

A study of people with Down syndrome and Alzheimer's disease highlights the importance of amyloid. But it also shows that's not the only factor.

Anne Warde-UC Irvine • futurity
April 8, 2020 3 minSource

A model of half a face with an exposed brain sits on a table

Amyloid is a key feature of Alzheimer’s disease, but the accumulation of these sticky proteins may not be the only risk factor for developing Alzheimer’s disease.

Other, modifiable risk factors, such as the amount of fats in our blood and how efficiently our bodies generate energy could also play important roles, new research suggests.

One of the largest studies of Alzheimer’s disease in people with Down syndrome (DS-AD) reveals metabolic alterations in DS-AD are similar to those seen in late-onset Alzheimer’s disease (LOAD) among the general population.

“We found that people with Down syndrome, who also have Alzheimer’s disease, show a deficit in energy metabolism that is similar to people with Alzheimer’s disease in the general population,” says first author Mark Mapstone of the neurology department at the University of California, Irvine School of Medicine and member of the Institute for Memory Impairments and Neurological Disorders (UCI MIND).

“These findings suggest that the amyloid accumulation, which occurs from birth in Down syndrome, may not be the only factor determining Alzheimer’s risk.”

The study is one of the first large-scale blood-based investigation of metabolic factors associated with aging and cognitive status in adults with Down syndrome and Alzheimer’s disease. It was based on a large cohort of adults with Down syndrome who were enrolled in the Alzheimer’s Biomarker Consortium-Down Syndrome (ABC-DS), a multi-site, longitudinal cohort study of adults with Down syndrome over age 25.

“Disruption of metabolic function is a recognized feature of late onset Alzheimer’s disease,” says Mapstone. “Our discovery could open new avenues for preventing this metabolic deficit in all people at risk for the disease.

Down syndrome is the most common neurodevelopmental disorder affecting over 250,000 individuals in United States. People with Down syndrome have a very high risk of developing Alzheimer’s disease and nearly all have the brain pathology (amyloid plaques) of Alzheimer’s at death.

“Their risk is thought to come from the fact that they have three copies of chromosome 21, where a key gene that produces amyloid is found. Because they have three copies of the gene, instead of two, they overproduce amyloid which is the key pathology of Alzheimer’s disease,” says Mapstone.

“By studying Alzheimer’s risk in people with Down syndrome, we can understand how important amyloid is to the development of the disease.”

Funding for this study came, in part, from the National Institute on Aging and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Source: UC Irvine

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