Usefulness of α-synuclein as a Marker for Early Diagnosis of Parkinson's Disease in Skin Biopsy.
Condition: Parkinson Disease; Parkinsonian Disorders
MeSH terms: Parkinson Disease; Parkinsonian Disorders
Study type: Observational

Summary: 
      Parkinson's disease (PD) is a degenerative disease that can be difficult to diagnose. The
      clinicopathological studies had demonstrated a 76% accuracy in the clinical diagnosis of PD.

      At the beginning of PD is difficult for the clinician to distinguish from Parkinsonism Plus
      Syndromes (PPS) due to the similarity of symptoms and the lack of specific diagnostic tests.

      Specific biomarkers to help improve the accuracy of diagnosis and to separate these two
      entities are highly needed

      The histological hallmark for definite diagnosis of PD is the presence of fibrillar
      aggregates of phosphorylated alpha-synuclein called Lewy bodies (LBs) and Lewy neurites.
      Previous autopsy-based studies have revealed that alpha-synuclein is deposited in the
      peripheral autonomic nervous system including the enteric nervous system of the alimentary
      tract, cardiac plexus, adrenal medulla and skin.

      For this reason, in patients with parkinsonism, an alternative tool could be to demonstrate
      alpha-synuclein fibrillar aggregates in the skin, allowing early and appropriate diagnosis.
    

Detailed description: 
      Parkinsonism, the syndrome, is a common movement disorder, and Parkinson's disease, the most
      common cause of parkinsonism, is the second most prevalent neurodegenerative disease after
      Alzheimer's disease.

      The clinical diagnosis of PD is based on the presence of the four common features: tremor
      when the limb is at rest, resistance to passive movement of the joints (rigidity), slowness
      and paucity of movement (bradykinesia and akinesia) and postural abnormalities.

      Approximately 25 percent of patients who received an initial clinical diagnosis of PD are
      found to have parkinsonism as part of another disorder, such as one of the so-called
      Parkinsonism-Plus Syndromes (PPS) The number and complexity of PPS seem to be increasing.
      This, along with the lack of diagnostic tests, makes it difficult for the clinician to
      distinguish between disease types.

      Some characteristic clinical features are used for the differential diagnosis, this
      manifestations include early and severe postural instability, falls in the first year of
      onset, abnormal eye movements, autonomic dysfunction, cerebellar signs and upper motor neuron
      signs. The PPS respond poorly to antiparkinsonian medications and have a worse prognosis than
      does PD. In spite of these suggestive features, not all PD patients have the same
      progression, in some cases it is impossible to separate typical PD from PPS, especially at
      the early stage. In this context, biological markers must be of great usefulness for the
      differential diagnosis of these entities.

      Some reports have described early features of PD such as (SPECT) imaging of the dopamine
      transporter that demonstrated the reduction of dopamine transporter in the striatum body at
      the early stage of PD and degeneration of the cardiac sympathetic nerve at the beginning of
      the disease process of PD; this occurs before neuronal cell loss is present in the dorsal
      vagal nucleus; This fact accounts for reduced cardiac uptake of meta-iodobenzylguanidine
      (MIBG), a physiological analog of norepinephrine. However, these diagnostic methods are not
      often performed. Therefore, more sensitive methods are needed to help improve the accuracy of
      diagnosis of PD.
    

Intervention name(s): Biopsy of skin
Intervention type(s): Procedure
Intervention description(s): Under local anesthesia with 1% xylocaine, 4-mm punch biopsies with 3-mm depth, including the dermis and subcutaneous fat tissue, will undergone from two regions, neck and lower back.
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        The patients will be selected from the department of neurology and the office of the
        principal investigator.
      
Biospecimen description: 
      We are obtaining the skin of the participants, by biopsy using a punch 3-4 mm in retro
      auricular area.

      We are taking from affected subjects and his or her partner (the most husband or wife).
    
Keywords: Parkinson Disease; Parkinsonian Disorders; Lewy Bodies; alpha-Synuclein