Biomarkers play a crucial role in medical research; find out what they are and how they're used in Alzheimer's disease.
What is a biomarker?
Biomarkers (short for ‘biological markers’) are characteristics of the body that can be objectively measured(1) – like body temperature or blood pressure.
They play a crucial role in medical research, diagnosis of disease and treatment by (2):
Helping scientists to understand how diseases affect the body and to evaluate the efficacy and safety of medicines.
Providing doctors with vital information to diagnose and manage their patients’ health conditions more effectively.
Why are biomarkers important in Alzheimer’s Disease (AD)?
AD is a highly complex disease. However, the more we learn about biomarkers of AD, the more our understanding of the disease – and how to accurately diagnose and manage it – improves.
While biomarkers to confirm AD are not yet used routinely by doctors in the ‘clinical’ setting(3) (i.e. in management of their patients), they already play an important role in research.(4) Doctors and scientists are excited about the potential impact AD biomarkers could have on improving care for people with AD.
For example, it is hoped that biomarkers could help to:
Which biomarkers can be used to diagnose AD?
There are a number of biomarkers in AD, with the list growing alongside our knowledge of the disease. Two of the main hallmarks and earliest signs of AD are the ‘plaques’ and ‘tangles’ that develop in the brain, caused by the build-up of certain proteins. These established biomarkers accurately measure those proteins and provide an aid in AD diagnosis.(12)
How are these biomarkers currently tested?
Today, there are two main ways to measure AD biomarkers:
There are different types of brain scans – from CT and MRI scans to the more sophisticated PET scans. In AD, PET scans allow us to look at the brain to see if beta-amyloid plaques or tau tangles have formed, or to measure their growth since a previous scan.(2)
While brain scans have many benefits, they can be costly and time-consuming for those undergoing the tests.16 Some of them are minimally invasive, and some carry a very small risk associated with exposure to radiation.(17) Therefore, this form of testing may not be the most practical tool for widespread use.(16)
Cerebrospinal fluid testing
The cerebrospinal fluid (CSF) is a clear, watery fluid that surrounds the brain and spinal cord.
It is thought that the build-up of beta-amyloid plaques and tau tangles in the brain changes the amount of these proteins in the CSF.(18) By testing the level of beta-amyloid and tau proteins in the CSF, we can understand if AD is developing in the brain (14) and potentially detect the disease earlier.
A sample of the CSF is taken from a person’s lower back using a special needle,(18) in a procedure that is similar to a spinal anaesthesia (epidural) during childbirth.
If performed by healthcare professionals, the risks associated with this procedure are minimal; the most common side effects are headache and back soreness.(18)
How could biomarkers support earlier diagnosis in the future?
One of the priorities for scientists working in AD is to develop faster, less invasive and widely accessible blood tests to measure AD biomarkers.
With a blood test, there is potential to conduct AD testing on a much broader scale. Initially, it could enable doctors in the primary care setting (e.g. general practitioners) to determine if AD could be the cause of a person’s symptoms – and transfer them to specialist care for further tests to confirm a diagnosis. In the future, it may even support screening for AD before symptoms appear.
Thanks to the collaborative efforts of academics, research institutions and industry partners around the world, significant progress is already being made towards this goal.
Together with the community, we will continue to advance the scientific understanding of AD and other neurological disorders and find better ways to diagnose, monitor and treat these conditions. By bringing these pieces together, our hope for the future is to create a tomorrow where neurological disorders no longer limit human potential—to help preserve what makes people who they are.
1. Food and Drug Administration. What Are Biomarkers and Why Are They Important? Transcript [Internet; cited 2020 June 17]. Available from: https://www.fda.gov/drugs/cder-biomarker-qualiﬁcation-program/what-are-biomarkers-and-why-are-they-important-transcript.
2. Alzheimer’s Drug Discovery Foundation. Alzheimer’s Biomarkers, Explained. [Internet; cited 2020 June 17]. Available from: https://www.alzdiscovery.org/news-room/blog/alzheimers-biomarkers-explained. Khoury R, Ghossoub, E. Diagnostic biomarkers of Alzheimer’s disease: A state-of-the-art review. Biomark.
3. Khoury R, Ghossoub, E. Diagnostic biomarkers of Alzheimer’s disease: A state-of-the-art review. Biomark. Neuropsychiatry. 2019;1(100005):1-6.
4. Cummings J. The Role of Biomarkers in Alzheimer’s Disease Drug Development. Adv Exp Med Biol. 2019;1118: 29–61.
5. National Institute on Aging. How Is Alzheimer's Disease Diagnosed? [Internet; cited 2020 June 17]. Available from: https://www.nia.nih.gov/health/how-alzheimers-disease-diagnosed.
6. Bogdanovic, N. The Challenges of Diagnosis in Alzheimer’s Disease. US Neurology. 2018;14(1):15-16.
7. Humpel C. Identifying and Validating Biomarkers for Alzheimer's Disease. Trends Biotechnol. 2011;29(1):26-32.
8. Jack CR Jr, et al. NIA-AA Research Framework: Toward a Biological Deﬁnition of Alzheimer's Disease. Alzheimers Dement. 2018;14(4):535-562.
9. Wu L, Rosa-Neto P, Gauthier S. Use of biomarkers in clinical trials of Alzheimer disease: from concept to application. Mol Diagn Ther. 2011;15:313-25.
10. Blennow K, Zetterberg H, Fagan AM. Fluid biomarkers in Alzheimer disease. Cold Spring Harb Perspect Med 2012;2(9):1-23.
11. Molinuevo JL, et al. Current state of Alzheimer's ﬂuid biomarkers. Acta Neuropathologica 2018;136(6):821-53.
12. Clifford R Jack Jr, MD, David S Knopman, MD, et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol 2010; 9:119-28.
13. BrightFocus Foundation. Amyloid Plaques and Neuroﬁbrillary Tangles. [Internet; cited 2020 June 17]. Available from: https://www.brightfocus.org/alzheimers/infographic/amyloid-plaques-and-neuroﬁbrillary-tangles.
14. National Institute on Aging. What Happens to the Brain in Alzheimer’s disease? [Internet; cited 2020 June 17]. Available from: https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease.
15. Mandelkow EM, Mandelkow E. Biochemistry and Cell Biology of Tau Protein in Neuroﬁbrillary Degeneration. Cold Spring Harb Perspect Med. 2012; 2(7):1-25.
16. Wittenberg R et al. Economic impacts of introducing diagnostics for mild cognitive impairment Alzheimer's disease patients. Alzheimers Dement (N Y). 2019; 5: 382–387.
17. NHS. PET scan. [Internet; cited 2020 June 29]. Available from: https://www.nhs.uk/conditions/pet-scan/.
18. Alzheimer’s Society. Having a lumbar puncture. [Internet; cited 2020 June 17]. Available from: https://www.alzheimers.org.uk/research/take-part-research/lumbar-puncture.