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Biomarkers of Parkinson’s Disease

Parkinson’s disease (PD) is a devastating disease that progressively affects the control of movement and also manifests in a wide range of other problems for patients (1). It is named after Dr. James Parkinson, who first characterised the condition in 1817 (2). PD is a progressive neurological condition and is caused by the death of dopamine-containing cells in the brain resulting in nerve messages to the muscles becoming slowed and abnormal (3). It is the second most common neurodegenerative disorder (4), affecting one person in every 500 (3). PD is more common in people aged 50 or over, however one in twenty affected individuals is under 40 (3). The frequency of PD increases with age with approximately 5 in 1,000 people in their 60s and 40 in 1,000 people in their 80s having PD (5). Therefore, PD is affecting an increasing number of individuals due to the fact that people are generally living longer nowadays.

In recent times, there has been a surge of interest in the identification and validation of biomarkers relevant to PD. Reliable Parkinson’s disease biomarkers would likely have application in the diagnosis of early PD (4) and in the identification of individuals at risk of developing PD (6). Such biomarkers can be studied in blood, serum, plasma, CSF and urine (6). Although further research will be required to identify reliable biomarkers for Parkinson’s disease, recent work in this area has led to a number of neurochemical and genetic biomarkers being proposed as having utility in the diagnosis of PD.

Several studies have shown that patients diagnosed with PD have significantly lower α-synuclein levels in their CSF. Furthermore, levels of DJ-1 have been reported to be decreased in the CSF of patients with PD (4). Other CSF markers that could potentially differentiate patients with PD include β-amyloid 1-42, total Tau, and IL-8 (4). It has also been reported that increased plasma concentrations of IL-6 in men correlates with an increased risk of developing PD (4). More recently, observed increases in the levels of IL-10 have led to the suggestion that immunological disturbances are involved in patients with PD (4). The potential of IL-10 as a biomarker for Parkinson’s disease will require further investigation.

Genetic testing for such common gene mutations in LRRK2, responsible for 1%-2% of sporadic cases of PD, may evolve into a valuable screening tool (4). Uric acid levels have been demonstrated to be significantly reduced in patients with PD. Moreover, higher urate levels in the blood and CSF could decrease the risk of PD and predict slow progression (4). In a study of 236 patients, low levels of low-density lipoprotein were associated with a 3.5 times higher than expected risk of developing PD and a follow up study confirmed the association between low cholesterol levels and the risk of Parkinson’s (4).

In spite of these recent advances in the understanding of the pathogenesis of PD, a major future goal in this area will be the identification and validation of robust biomarkers of neurodegenerative disorders such as PD. Such preclinical biomarkers are essential in identifying at risk populations that might be potential targets for neuroprotective or disease modifying therapeutic strategies (4). Furthermore, the identification of such biomarkers will improve our overall understanding of the pathogenesis of Parkinson’s disease and other meurodegenerative disorders (1).

1. http://www.ninds.nih.gov/about_ninds/plans/nihparkinsons_agenda.htm

2. http://www.nhs.uk/conditions/Parkinsons-disease/Pages/Introduction.aspx

3. http://www.parkinsons.org.uk/about_parkinsons/what_is_parkinsons.aspx

4. Yuncheng Wu, Weidong Le and Joseph Jankovic (2011) Preclinical Biomarkers of Parkinsons Disease. Neurological Review 68 (No. 1) 22-30

5. http://www.patient.co.uk/health/Parkinson’s-Disease.htm

6. Graeber MB (2009) Biomarkers for Parkinson’s disease. Experimental Neurology 216 (2) 249-53

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