Recent advances in blood-based biomarkers have led to headlines about potential blood tests for diseases such as Alzheimer’s. In this blog post, we explore how researchers can use biomarkers to see dementia-related changes in the brain, track disease onset and progression, and test the effectiveness of promising drugs and potential treatments.
Biomarkers (or biological markers) are measurable indicators of what is happening in your body. These can be found in the blood, other body fluids, organs, and tissues. Some can even be measured digitally.
Typically, there are several definitions of a biomarker. However, the World Health Organisation defines a biomarker as ‘any measurement reflecting an interaction between a biological system and a potential hazard, which may be chemical, physical, or biological. The measured response may be functional and physiological, biochemical at the cellular level, or a molecular interaction.’
This means that biomarkers are not medical symptoms, such as a high temperature indicating fever. But an increased heart rate as a result of physical exertion is a biomarker. The increased heart rate is a physiological response to the exercise.
Biomarkers are important because they help doctors and researchers to monitor and track health conditions, as well as diagnose different diseases. They can thus be used to find out what will happen to you when you use a particular treatment – or don’t use the treatment – and the risk of developing certain medical conditions.
Current research studies show that biomarkers offer one of the most promising paths for the diagnosis of dementia. They help clinicians detect early brain changes, better understand how risk factors are involved, identify participants who meet particular requirements for certain clinical trials, and track responses to physical interventions like exercise and other activities. When combined with other tests, these biomarkers can also help to determine whether a person might have, or be at risk of developing, dementia. However, no single test can alone diagnose the conditions. Biomarkers are only one part of a complete assessment.
The following information notes how some of these biomarkers are used for research purposes, in addition to diagnosis.
Types of biomarkers and tests
Several types of brain scan enable scientists and doctors to see different factors that may help diagnose dementia or related diseases. Doctors use brain scans to find evidence of other sources of damage, such as tumour or stroke that may aid in diagnosis. Brain scans used to help diagnose dementia include CT, MRI, and PET scans.
COMPUTERISED TOMOGRAPHY (CT)
A CT scan is a type of X-ray, which uses radiation to produce images of the brain or other parts of the body. A head CT can show shrinkage of brain regions that may occur in dementia, as well as signs of other possible sources of disease, such as an infection or blood clot. A doctor might compare the size of certain brain regions to previous scans or to what would be expected for a person of the same age and size to detect dementia.
MAGNETIC RESONANCE IMAGING (MRI)
MRI uses magnetic fields and radio waves to produce detailed images of body structures, including the size and shape of the brain and brain regions. Similar to CT scans, MRIs can show whether areas of the brain have shrunk. Repeat scans can show how a person's brain changes over time. Evidence of shrinkage may support a diagnosis of neurodegenerative dementia but cannot indicate a specific diagnosis. MRI also provides a detailed picture of brain blood vessels. Before making a dementia diagnosis, doctors view MRI results to rule out other causes of memory changes such as brain bleed or build-up of fluid in the brain. In research, various types of MRI scans are used to study the structure and function of the brain in both healthy ageing and in dementia disease.
POSITRON EMISSION TOMOGRAPHY (PET)
PET uses small amounts of a radioactive substance called a tracer to measure specific activity in different parts of the brain. PET scans take pictures of the brain, revealing regions of normal and abnormal chemical activity. There are several types of PET scan that can help doctors diagnose dementia.
- Amyloid PET scans measure abnormal deposits of a protein called beta-amyloid. Higher levels of beta-amyloid are consistent with the presence of amyloid plaques, a hallmark of dementia. This type of scan is often used in research settings to identify those at risk of developing dementia-related conditions and to test potential treatments.
- Tau PET scans detect the abnormal accumulation of the tau protein. Tau forms tangles within nerve cells in dementia-related conditions. Tau PET scans are more often used in research settings to help identify people who are at risk of developing dementia and test potential treatments.
- Fluorodeoxyglucose (FDG) PET scans measure energy use in the brain. Glucose, a type of sugar, is the primary source of energy for cells. Studies show that people with dementia often have abnormal patterns of decreased glucose use in specific areas of the brain. In a clinical setting, FDG PET scans may be used if a doctor strongly suspects the occurrence of frontotemporal dementia.
A major barrier to developing new drugs for dementia-related disease is that it is hard to identify patients who are in the early stage of the disease. In such cases, fluid biomarkers, especially blood and plasma-based biomarkers, have become the most attractive tool as they are non-invasive, relatively economical, and easy to obtain. Advances in the search of blood-based biomarkers are classified according to the topics related to the main hallmarks of the dementia disease such as inflammation, amyloid and tau deposition, synaptic degeneration, and oxidative stress. Identifying changes in blood and plasma can be very useful in formulating new diagnostic and treatment proposals in the field of dementia.
CEREBROSPINAL FLUID BIOMARKERS (CSF)
CSF is a clear fluid that surrounds the brain and spinal cord, providing protection and insulation. Proteins and other substances made by brain cells can be detected in CSF. Measuring changes in the levels of these substances can help diagnose neurological problems like dementia. The most widely used CSF biomarkers for Alzheimer's disease – one form of dementia – is beta-amyloid 42. In clinical practice, CSF biomarkers are valuable tools for early detection of a neurodegenerative disease and to assess the impact of experimental medications.
A genetic test is a type of medical test that analyses DNA from blood or saliva to determine a person's genetic makeup. A number of genetic combinations may change the risk of developing a disease that causes dementia. Such tests are not routinely used in clinical settings to diagnose or predict the risk of developing dementia. However, a neurologist or other medical specialist may order a genetic test in certain situations, such as when a person has an early age of onset with a strong family history of dementia.
It is perhaps in the area of treatments that biomarkers currently have the most exciting potential benefit. The use of biomarkers is enabling scientists to make great progress in identifying potential new treatment targets and ways to prevent or delay dementia – and to test whether treatments are having the desired effect on particular biomarkers. These and similar advances have been possible only because of the thousands of volunteers who have actively participated in clinical trials and studies.
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21 September 2022
Last month, dementia researchers from around the world flocked to San Diego for the latest edition of the Alzheimer’s Association International Conference (AAIC) – the world’s biggest dementia research conference. Among the attendees was Dr Ludovica Griffanti, an Alzheimer’s Association Research Fellow at Oxford University who co-leads DPUK’s imaging pipelines project. On World Alzheimer’s Day 2022, Dr Griffanti picks out some of her highlights from the packed conference programme.