Newswise —
Scientists at Karolinska Institutet in Sweden have made a breakthrough in the early detection and treatment of Alzheimer's disease. They have identified a specific type of sugar molecule in the blood that is linked to the level of tau protein, a key player in the development of severe dementia. This discovery opens the door to a cost-effective and reliable screening method that could accurately predict Alzheimer's onset up to a decade in advance. The findings of this study have been published in the prestigious journal Alzheimer's & Dementia.
"The role of glycans, which are structures composed of sugar molecules, has been relatively understudied in the field of dementia research," explains Robin Zhou, the lead author of the study and a medical student and affiliated researcher at the Department of Neurobiology, Care Sciences, and Society (NVS) at Karolinska Institutet. "Our study reveals that the levels of glycans in the blood are altered in the early stages of Alzheimer's disease. This suggests that a simple blood test combined with a memory test could potentially predict the risk of developing Alzheimer's disease."
Alzheimer's disease is characterized by the degeneration of neurons in the brain, believed to be caused by the abnormal buildup of amyloid beta and tau proteins. Clinical trials have shown that early intervention is crucial, as treatment should ideally begin during the early stages of the disease, before extensive neuron loss has occurred, in order to effectively reverse the pathological process before it becomes irreversible.
More blood biomarkers needed
There is both a practical and a financial need for non-invasive screening methods for Alzheimer’s. Markers in blood are preferable, as taking samples of the cerebrospinal fluid is more difficult and brain imaging is expensive.
A recent study conducted by researchers at Karolinska Institutet has demonstrated that the presence of a specific glycan structure in blood, known as bisected N-acetylglucosamine, can serve as a predictive marker for Alzheimer's disease. This finding suggests that the level of this glycan structure in blood could potentially be used as an indicator of the risk of developing Alzheimer's disease. This discovery further underscores the potential of blood-based markers as a reliable and accessible method for early screening and detection of Alzheimer's disease, which could aid in earlier intervention and management of this neurodegenerative condition.
The research team at Karolinska Institutet has previously established a correlation between the levels of tau protein and glycans in individuals with Alzheimer's disease, but these investigations were conducted using cerebrospinal fluid samples. Glycans are sugar molecules that are located on the surface of proteins, which are essential components of living organisms, and they play a crucial role in determining the localization and function of these proteins in the body. This indicates that glycans may have a significant influence on the development and progression of Alzheimer's disease, and further research into their role in this neurodegenerative condition could potentially lead to new insights and potential therapeutic targets for managing Alzheimer's disease.
By measuring blood glycan levels the researchers found that individuals with matching levels of glycans and tau were over twice as likely to develop Alzheimer’s-type dementia.
The corresponding author of the study, Sophia Schedin Weiss, who is a docent at NVS, Karolinska Institutet, stated that their research findings revealed that a straightforward statistical model, which incorporates blood glycan and tau levels, the APOE4 risk gene, and a memory test, could predict Alzheimer's disease with an accuracy rate of 80% nearly ten years before the manifestation of symptoms such as memory loss. This suggests that a combination of these factors could serve as a reliable predictive tool for early detection of Alzheimer's disease, offering the potential for timely interventions and improved management of this devastating condition. The integration of blood glycan and tau levels, genetic information, and cognitive assessments could pave the way for a simple and effective screening procedure to identify individuals at risk of Alzheimer's disease at an early stage. Further research and validation of this model could have significant implications for the diagnosis and management of Alzheimer's disease in clinical practice.
17-year follow-up
The findings of the study are derived from a cohort of 233 participants who were part of the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). The samples used in the study were collected between 2001 and 2004, and the participants were closely monitored over a period of 17 years with regards to factors such as memory loss and the presence of dementia. Follow-up assessments were conducted at regular intervals of three to six years, providing a long-term perspective on the development of Alzheimer's disease and related cognitive changes in the study population. The extensive duration of the follow-up period and the comprehensive nature of the data collected provide a robust foundation for the research findings, enhancing the validity and reliability of the conclusions drawn from the study.
The researchers involved in the study plan to further analyze blood samples from the remaining participants in the SNAC-K study, as well as from participants in other aging studies conducted both within and outside of Sweden. This expanded analysis will help to validate and strengthen the findings, as it will involve a larger and more diverse sample size. By examining blood samples from multiple cohorts, the researchers aim to confirm the association between blood glycan levels and the risk of developing Alzheimer's disease, and to assess the generalizability of their findings to different populations. This approach will contribute to the robustness and reliability of the research findings, and may potentially pave the way for the development of a simple and cost-effective screening method for early diagnosis of Alzheimer's disease in clinical practice.
Dr. Schedin Weiss highlights that the research team is collaborating with researchers in primary care in Sweden to evaluate various biomarkers for dementia, including glycans in the blood, at primary health care centers. The aim is to assess the potential of blood glycans as a valuable complement to current screening methods for detecting Alzheimer's disease early. By working in partnership with primary care settings, where early detection and intervention are crucial, the researchers aim to contribute to the development of reliable and cost-effective screening methods for Alzheimer's disease that can be implemented in routine clinical practice. The hope is that blood glycans may emerge as a promising biomarker for early detection of Alzheimer's disease, thereby improving the chances of timely diagnosis and treatment initiation.
The study was carried out by a team of researchers led by Lars Tjernberg, affiliated with the Division of Neurogeriatrics at Karolinska Institutet, in collaboration with the Aging Research Centre at Karolinska Institutet, the Stockholm Gerontology Research Center, and Karolinska University Hospital. This collaborative effort involved experts from multiple institutions, bringing together diverse expertise and resources to conduct a comprehensive investigation into the association between blood glycan levels and Alzheimer's disease risk. Such interdisciplinary collaborations are crucial for advancing scientific knowledge and translating research findings into meaningful clinical applications for the benefit of patients and healthcare practices.
It was financed by the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, Stiftelsen Gamla Tjänarinnor, the Gun and Bertil Stohnes Foundation, the Swedish Alzheimer’s Foundation, Stiftelsen Dementia, JPND, Vinnova and Region Stockholm (ALF). The researchers report no conflicts of interest.
Publication: “A glycan epitope correlates with tau in serum and predicts progression to Alzheimer’s disease in combination with APOE4 allele status”. Robin Ziyue Zhou, Davide Liborio Vetrano, Giulia Grande, Frida Duell, Linus Jönsson, Erika J Laukka, Claudia Fredolini, Bengt Winblad, Lars Tjernberg, Sophia Schedin-Weiss. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, online 12 April 2023.
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