White hand drawn cell and brain illustrations on a purple background

Biomarkers: Changing the way Alzheimer’s disease is diagnosed

Published 20 July 2020

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 measured1 – like body temperature or blood pressure.

They play a crucial role in medical research, diagnosis of disease and treatment by:2

Microscope illustration with a background of a DNA helix and DNA nucleotide

Helping scientists to understand how diseases affect the body and to evaluate the efficacy and safety of medicines.

An illustration of a doctor holding a clipboard, talking to a couple, the man has a walking stick

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’ setting3 (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:

  • <p><b>Support earlier, more accurate diagnosis</b><br/> Today, the diagnosis of AD is largely based on symptoms that individuals and their families describe to their doctor and measures like memory tests, as well as tests to exclude other illnesses.<sup>5</sup> However, because symptoms are less noticeable in the early stages or are attributed to normal aging, an accurate early diagnosis can be challenging.<sup>6</sup></p>  <p>Biomarker testing could overcome this challenge, as changes in AD biomarkers occur decades before symptoms are noticed.<sup>7,8</sup></p>

    Support earlier, more accurate diagnosis
    Today, the diagnosis of AD is largely based on symptoms that individuals and their families describe to their doctor and measures like memory tests, as well as tests to exclude other illnesses.5 However, because symptoms are less noticeable in the early stages or are attributed to normal aging, an accurate early diagnosis can be challenging.6

    Biomarker testing could overcome this challenge, as changes in AD biomarkers occur decades before symptoms are noticed.7,8

  • <p><b>Monitor the progression of the disease</b><br/> Measuring changes in biomarkers can help us to understand how quickly a person’s disease is advancing – and, potentially, predict how it may develop in the future.<sup>9,10</sup></p><p>Biomarkers are already used for this purpose in clinical trials.<sup>9</sup> Broader use of biomarker monitoring could help doctors to build personalised care plans for people living with AD.<sup>11</sup></p>

    Monitor the progression of the disease
    Measuring changes in biomarkers can help us to understand how quickly a person’s disease is advancing – and, potentially, predict how it may develop in the future.9,10

    Biomarkers are already used for this purpose in clinical trials.9 Broader use of biomarker monitoring could help doctors to build personalised care plans for people living with AD.11

  • <p><b>Measure response to treatment</b><br/> Measuring changes in AD biomarkers may also allow doctors to detect early signs that a person is - or is not - responding to a medicine,<sup>10</sup> and adjust their treatment as needed. This plays an important role in clinical trials today and will become more important for doctors and people with AD as disease-modifying treatments become available.<sup>2,11</sup></p>

    Measure response to treatment
    Measuring changes in AD biomarkers may also allow doctors to detect early signs that a person is - or is not - responding to a medicine,10 and adjust their treatment as needed. This plays an important role in clinical trials today and will become more important for doctors and people with AD as disease-modifying treatments become available.2,11

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

  • Identifying the presence of beta-amyloid plaques and tau tangles in the brain helps to more objectively diagnose and monitor the progression of AD.
    Identifying the presence of beta-amyloid plaques and tau tangles in the brain helps to more objectively diagnose and monitor the progression of AD.
  • Identifying the presence of beta-amyloid plaques and tau tangles in the brain helps to more objectively diagnose and monitor the progression of AD.
    Identifying the presence of beta-amyloid plaques and tau tangles in the brain helps to more objectively diagnose and monitor the progression of AD.

How are these biomarkers currently tested?

Today, there are two main ways to measure AD biomarkers:

An illustration of a female scan operator giving a male patient a CT brain scan

Brain scanning
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

A simple diagram of the human body showing the brain and spinal cord.  A call out image shows a needle extracting fluid from the base of the spine

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 brain14 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?

An illustration of a male nurse performing a blood test on a woman

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.

References

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.

Tags: Science, Neuroscience, Alzheimer's disease