Biomarkers

What are common types of biomarkers in Parkinson’s?

Biomarkers are classified as clinical, imaging, pathological, biochemical and genetic.

1. Genetic biomarkers: Specific genetic mutations or variations, such as mutations in the LRRK2, SNCA, PINK1, PARK2 (Parkin) or GBA genes, are associated with an increased risk of Parkinson’s (i.e. risk does not equate to certainty of Parkinson’s). Genetic testing can identify individuals at higher risk and provide insights into the potential for individualised care for that ‘type’ of Parkinson’s, as well as early intervention strategies if you are a carrier.
2. Imaging biomarkers, or the use of structural and functional neuroimaging techniques, including MRI, PET (Positron Emission Tomography), and fMRI (functional MRI), can reveal brain changes associated with Parkinson’s, such as multiple system atrophy, metabolic alterations, and abnormal neural activity patterns. Dopamine transporter imaging (DaTscan) is a type of SPECT (Single Photon Emission Computed Tomography) imaging that measures dopamine transporter levels in the brain. Reduced dopamine transporter binding indicates dopamine neuron loss, which occurs in Parkinson’s.
3. Biochemical biomarkers exist in body fluids and tissues, including blood, saliva, cerebrospinal fluid (CSF), and biopsies. Biomarkers found in the CSF, such as α-synuclein, tau protein, and beta-amyloid, are being studied to assess neurodegenerative processes in Parkinson’s. Changes in these biomarkers may indicate progression or severity. The current biomarker breakthrough is the α-synuclein seeding amplification assay (αSyn-SAA) which mixes CSF with some chemicals to test if your α-synuclein is prone to clumping.
4. Clinical biomarkers look at a constellation of symptoms that may indicate a Parkinson’s diagnosis. These include slowness (bradykinesia), resting tremor (in around 70% of people with Parkinson’s) and muscle rigidity. However, these well-known motor symptoms only appear over 60% of dopaminergic-producing neurons are already lost. For earlier PD diagnosis, some non-motor symptoms may help detect prodromal (early) PD. In addition, several other non-motor symptoms are common in PD, including unexplained mood changes (e.g. anxiety, depression, apathy) orthostatic hypotension (dizziness), continence issues and sexual dysfunction. Although having a single symptom is a low predictor, when multiple symptoms co-occur, there should be reason for further investigation.
   1. Hyposmia/Anosmia is reduced or complete loss of your sense of smell. Olfactory dysfunction has been linked to PD in studies from as early as 1975! It is thought that the alpha-synuclein first starts clumping in the olfactory bulb. Changes to the sense of smell may happen decades before motor symptoms start.
   2. Rapid Eye Movement (REM) Sleep Behaviour Disorder is estimated to affect up to 60 % of people with Parkinson’s. It can occur several years before the onset of motor symptoms. This parasomnia results in the person calling out and acting out in their dreams.
   3. Constipation is the most common symptom of autonomic dysfunction in Parkinson’s. A slowed GI tract impacts medication uptake and overall wellbeing in people living with Parkinson’s. Management of constipation has many benefits for a person living with Parkinson’s and should be a priority due to the serious outcomes if left untreated.

The future of biomarkers

Why can’t we use something easier, like serum biomarkers (blood or saliva)? Although a reliable CSF or imaging biomarker would be extremely valuable for a PD diagnosis, the ultimate goal is to find a serum biomarker that would not require the expertise for invasive procedures or expensive imaging equipment. Research continues to explore and validate these biomarkers to improve early diagnosis, monitor progression, and evaluate the effectiveness of treatments in Parkinson’s. Incorporating biomarkers into clinical practice holds promise for personalised medicine approaches and advancing therapeutic strategies for individuals affected by Parkinson’s. Remember, always consult a healthcare professional for personalised advice and management strategies.