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People with Down syndrome and Alzheimer’s show similar changes in metabolic processes as people with late stage disease

People with Down syndrome who are at risk for or have Alzheimer’s disease experience disruption in the energy metabolism processes in their cells, similar to those seen in late stage disease, according to study from the NIH-funded Alzheimer’s Biomarkers Consortium–Down Syndrome (ABC-DS) study. The findings also suggest potential blood-based biomarkers measuring metabolic factors could be useful for tracking progression of disease from cognitively unaffected to mild cognitive impairment and Alzheimer’s.

3-D microscopic illustration of cell membrane that shows the lipid layer of the membrane in yellow and particles in blue moving from inside the cytoplasm and through the membrane
3-D illustration of cell membrane and lipid bilayer

According to the authors, this research is one of the first, large-scale blood-based investigations of metabolic factors — the biochemical reactions in cells used to create and use energy — associated with aging and cognitive status in adults with Down syndrome and Alzheimer’s. The findings were published in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. 

Recognizing that disruption of metabolic function is a feature of late onset Alzheimer’s disease, the research team sought to find out if similar metabolic pathways exist in adults with Down syndrome. People who have Down syndrome are at higher risk for Alzheimer’s disease, and tend to begin to show symptoms in their 50s and 60s.

The team examined blood samples from 292 participants from the ABC-DS study. The samples were from 38 individuals who had Alzheimer’s, 43 who had mild cognitive impairment, and 211 who were cognitively unaffected and stable.

Using mass spectrometry, the researchers measured for 8,805 metabolic features in the blood samples. They found 180 metabolites were differentially expressed among the groups. From those features, the researchers used statistical and machine learning models to classify characteristics within the groups. They found strong evidence of fatty acid and cellular energy metabolic differences, which they suggest might underlie Alzheimer’s-related clinical and cognitive decline in people with Down syndrome. The analysis also produced findings consistent with research showing the involvement of lipid metabolism in late onset Alzheimer’s.

The researchers note that a future prospective study to identify longitudinal changes in metabolism within individuals may help further understanding how Alzheimer’s evolves in people with Down syndrome.

Families of people with Down syndrome who may be interested in participating in the ABC-DS study can find more information on the NIA website.

ABC-DS clinical, cognitive, and biomarker (fluid and imaging) data and biospecimen samples are available to researchers.

ABC-DS is funded by NIA and the NIH’s National Institute for Child Health and Human Development (U01 AG051406 and U01 AG051412). Additional funding came from NIH grants P50AG008702, P30AG062421, P50AG16537, P50AG005133, P50AG005681, P30AG062715, U54HD090256, U54HD087011, UL1TR001873, UL1TR002373, UL1TR001414, UL1TR001857, UL1TR002345, U24AG21886.

These activities relate to NIA’s AD+ADRD Research Implementation Milestone 9.F, “Initiate studies to develop minimally invasive biomarkers for detection of cerebral amyloidosis, AD and AD-related dementias pathophysiology.”

Reference: Mapstone M, et al. Metabolic correlates of prevalent mild cognitive impairment and Alzheimer's disease in adults with Down syndrome. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. 2020;12(1):e12028. doi: 10.1002/dad2.12028.