The new bio-markers of Parkinson’s disease

Thanks to scientists, new biomarkers for Parkinson’s disease (PD) were found recently. The new biomarkers are β-amyloid 1-42 (Aβ1-42), total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181), and α-synuclein. The investigators found that these biomarkers are relatively lower in cerebrospinal fluid of drug naïve-patients compared to healthy controls. The researchers added that PD can be predicted by Aβ1-42 and P-tau181 whereas the severity of motor dysfunction can be found from T-tau and α-synuclein (1).

The data obtained was an effort from Parkinson’s Progression Markers Initiative (PPMI). It is an international study aimed at identifying biomarkers of progression in PD. The study involved 400 drig naïve patients with PD at early stage and 200 healthy controls from United States, Europe and Australia.

What is Parkinson’s disease?

Parkinson’s disease or idiopathic Parkinson’s disease is one of the Parkinsonian disorders along with atypical Parkinsonian disorder (APD). Either of the two Parkinsonian disorders share common movement abnormalities such as

  1. Hypokinesia or diminished movement activity (bradykinesia, slowness of movement)

  2. Rest tremor.

  3. Rigidity (muscle stiffness).

  4. Loss of postural reflexes.

  5. Flexes posture.

  6. The freezing phenomenon.

Out of the two Parkinsonian disorders, PD is most prevalent affecting a considerable number of patients (2).

The new biomarkers

  • Aβ1-42: It is the major component of amyloid plaques particularly senile plaques. These senile  plaques are usually found accumulated in neurons of Alzheimer’s patients or in general aging (3). Aβ proteins are 39-42-amino acid long and are derived from amyloid precursor protein (APP; 4).

  • T-tau and P-tau-181: Tau proteins are involved in the stabilization of microtubules in neurons. Their presence is abundant only in neurons of central nervous system (5). Tau is generally involved in Alzheimer’s disease where its phosphorylation causes neuronal plasticity and brain lesions. Hyperphosphorylated tau proteins detach from microtubules, destabilize them and  compromise axonal transport (6).

  • α-synuclein: It is a member of synuclein family of proteins along with β- and γ-synuclein. These proteins are abundantly expressed in nervous system and present at presynaptic terminals, but not in vesicles. They were found to involve in control of neurotransmission. This protein also causes disruptions in cellular homeostasis and neuronal death. It is also thought to have serious effects on neighbouring cells (7).

References

  1. Kang JH, Irwin DJ, Chen-Plotkin AS, et al. Association of Cerebrospinal Fluid β-Amyloid 1-42, T-tau, P-tau181, and α-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease. JAMA Neurol. 2013 Aug 26. doi: 10.1001/jamaneurol.2013.3861. [Epub ahead of print].

  2. Constantinescu R, Mondello S. Cerebrospinal Fluid Biomarker Candidates for Parkinsonian Disorders. Front Neurol. 2012; 3: 187.

  3. http://www.anaspec.com/products/product.asp?id=33188

  4. Cras P, Kawai M, Lowery D, et al. Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7552-6.

  5. http://www.news-medical.net/health/Tau-Proteins-What-are-Tau-Proteins.aspx

  6. Hampel H, Blennow K, Shaw LM, et al. Total and phosphorylated tau protein as biological markers of Alzheimer’s disease. Exp Gerontol. 2010 Jan;45(1):30-40.

  7. Stefanis L. α-Synuclein in Parkinson’s Disease. Cold Spring Harb Perspect Med. 2012 February; 2(2): a009399.

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