Sugar Molecule Levels in Blood Could Predict Alzheimer’s Disease

A new study has found an association between levels of a sugar molecule and a key protein involved in Alzheimer’s disease (AD) in the blood, potentially paving the way for the development of a simple, non-invasive screening test to predict risk of AD. The research is published in Alzheimer’s & Dementia.

A need for Alzheimer’s screening methods

AD is a neurodegenerative disease, in which the neurons of the brain degrade and die. It is thought to be caused by the accumulation of abnormal and misfolded proteins, tau and amyloid beta, within the brain. This can lead to problems with speech and language, memory loss and cognitive decline.

It is estimated that, in 2023, 6.7 million Americans over the age of 65 are living with AD. There is currently no cure or treatments to slow the progression of the disease, though there are some drugs available to help manage or ease its symptoms. Clinical trials have shown that successful treatments need to be administered early in the course of disease progression in the brain in order to reverse the process before too many neurons are lost.

Improved screening methods may help to detect those at risk of the disease earlier. Current methods, such as sampling cerebrospinal fluid (CSF) – the fluid that surrounds our brain and spinal cord – and brain imaging, can be expensive and difficult to perform. Non-invasive screening methods, such as detecting biomarkers in the blood, would provide both practical and financial benefits.

In a previous study, researchers from the Karolinska Institute in Sweden demonstrated an association between the levels of a sugar molecule and tau proteins in CSF. Now, these researchers explore whether this association can also be found in the blood, potentially laying the foundations for a simple screening test able to predict AD onset 10 years in advance.

Potential blood biomarker

The researchers monitored levels of a sugar molecule, or glycan, in the blood known as bisected N-acetylglucosamine. Glycans are found on the surface of proteins and help to direct their function as well as their location in the body.

Data was collected from blood samples taken from 233 participants in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Samples were collected from 2001–2004, and the participants were regularly monitored every 3 to 6 years, assessing them for factors such as memory loss and dementia over a total period of 17 years. The researchers found that people with matching levels of tau and glycans in their blood had over twice the risk of developing AD.

“We also show that a simple statistical model that take into account blood glycan and tau levels, the risk gene APOE4 and a memory test, can be used to predict AD to a reliability of 80% almost a decade before symptoms such as memory loss appear,” said Dr. Sophia Schedin Weiss, senior author of the study and associate professor in medical biochemistry at the Karolinska Institute.

Expanding biomarker evaluation

“The role of glycans, structures made up of sugar molecules, is a relatively unexplored field in dementia research,” said Robin Zhou, first author of the study, medical student and affiliated researcher at the Karolinska Institute. “We demonstrate in our study that blood levels of glycans are altered early during the development of the disease. This could mean that we’ll be able to predict the risk of AD with only a blood test and a memory test.”

The researchers will now be analyzing blood samples from the remaining participants of the SNAC-K study as well as from participants of other aging studies in and outside Sweden.

“We’re collaborating with researchers in primary care in Sweden to evaluate different biomarkers for dementia at primary health care centres,” said Weiss. “We hope that glycans in the blood will prove to be a valuable complement to current methods of screening people for AD that will enable the disease to be detected early.”

Reference: Zhou RZ, Vetrano DL, Grande G, et al. A glycan epitope correlates with tau in serum and predicts progression to Alzheimer’s disease in combination with APOE4 allele status. Alzheimer’s Dement. 2023. doi: 10.1002/alz.13024

This article is a rework of a press release issued by the Karolinska Institute. Material has been edited for length and content.