Down Syndrome/Alzheimer’s Link?

Plaque formation in AD. Naturally occurring amyloid precursor protein (green and white) is cleaved by beta-secretase (pink), freeing the amyloid-beta protein fragment (green).

Beta Testing

Down Syndrome Study may Reveal an Early Biomarker of Alzheimer’s Disease

By Sver Aune

People with Alzheimer’s Disease (AD) develop amyloid-beta plaques and neurofibrillary tangles that cause progressive neuron loss and dementia. A clinical diagnosis of AD is typically made after this process begins, when preventive treatment may be less effective. While advances have been made in AD detection, investigators are searching for an early diagnostic biomarker that could allow clinicians to identify and treat those at greater risk for developing AD.

Intriguingly, a biomarker for AD might be discovered in people with Down Syndrome (DS). Since 1983, due to increased education about DS and higher rates of home and medical care, life expectancy for people with DS has risen from 25 years to nearly 60. This recent increase has likely contributed to the emergence of a new clinical phenomenon: people with DS who reach their thirties begin to develop AD pathology in their brains at alarming rates. As many as 80percent of people with DS who reach the age of 60 have signs of AD.

While research has not yet linked an early biomarker to AD, the cause of early-onset AD in people with DS (DS-AD) could indeed lie in their genes. Down Syndrome is caused by a partial or complete extra copy of chromosome 21. Chromosome 21 carries the gene for amyloid precursor protein that is implicated in increased amyloid-beta plaque deposition in the brains of people with AD or DS-AD. However, differences may exist between the two conditions. In brains of people with DS, diffuse amyloid-beta deposits appear during childhood or early adulthood, while these deposits appear at an older age in those with late-onset AD. Mutations in chromosome 21 or other chromosomes are seen in a small fraction (about 10percent) of cases of idiopathic AD.

“The Alzheimer’s field has about 100 clinical trials going on. There are exactly two for people with DS and AD,” says Lotta Granholm, Ph.D., D.D.S., former Director of the MUSC Center on Aging. To help bridge this gap, Granholm has commenced a biomarker study that enables physicians statewide to collect potential biomarkers for early-onset AD from the blood of DS patients.1

Entering people with intellectual disabilities in clinical trials has been a historically delicate undertaking. Experts plan to advance their research responsibly. Granholm recently helped organize a workshop sponsored by the Alzheimer’s Association, the Linda Crnic Institute for Down Syndrome, and the Global Down Syndrome Foundation, which invited AD and DS experts from MUSC and across the country to share their collective knowledge about the links between DS and AD and to offer criteria for conducting AD clinical trials in people with DS. The workshop was covered in the Washington Post1 and was the subject of a recent article in the journal Alzheimer’s & Dementia.2

To aid research on aging, the MUSC Carroll A. Campbell, Jr. Neuropathology Laboratory accepts brain donations from people who have suffered from a variety of aging-related brain disorders, including Alzheimer's Disease and Down Syndrome, and serves clinicians and families in the entire state through the South Carolina Aging Research Network. 


1Kunkle, F. (2015, May 22) Why studying Alzheimer’s in people with Down Syndrome could help everyone. The Washington Post Retrieved from

2Hartley D, et al. Alzheimer’s and Dementia 2015;11(6):700-709.