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Alpha-Synuclein Skin Deposits Characterize Parkinson’s Disease Patients

By LabMedica International staff writers
Posted on 18 Mar 2022
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Image: Confocal microscope study of p-syn deposits in a dermal arteriole of a patient with PD (Photo courtesy of Dr. Alex Incensi)
Image: Confocal microscope study of p-syn deposits in a dermal arteriole of a patient with PD (Photo courtesy of Dr. Alex Incensi)

The detection of skin deposits of the neurodegenerative disease biomarker protein alpha-synuclein (p-syn) may be useful for the differential diagnosis of parkinsonism.

Parkinsonism is a clinical syndrome characterized by the four motor symptoms found in Parkinson's disease: tremor, bradykinesia (slowed movements), rigidity, and postural instability. As previous studies had reported the presence of phosphorylated p-syn skin deposits in Parkinson’s disease (PD) patients, but not in patients with parkinsonism due to tauopathies, a team of Italian investigators aimed to assess the presence of skin p-syn deposits in patients with taupathies such as progressive supranuclear palsy and corticobasal syndrome and PD.

PD is a slowly progressive disorder that affects movement, muscle control, and balance. It is the second most common age-related neurodegenerative disorder affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age.

Taupathies belong to a class of neurodegenerative diseases involving the aggregation of tau protein into neurofibrillary or gliofibrillary tangles (NFTs) in the human brain. Tangles are formed by hyperphosphorylation of the microtubule protein tau, causing the protein to dissociate from microtubules and form insoluble aggregates. Two taupathies that were of particular interest in the current study were:

Progressive supranuclear palsy (PSP) is a late-onset degenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty moving the eyes, and cognitive impairment. PSP may be mistaken for other neurodegenerative diseases such as PD, frontotemporal dementia, and Alzheimer's. The cause of the condition is uncertain, but involves accumulation of tau protein within the brain.

Corticobasal syndrome (CBS) is a rare neurodegenerative disease involving the cerebral cortex and the basal ganglia. It is characterized by marked disorders in movement and cognition, and is classified as one of the Parkinson plus syndromes. Diagnosis is difficult, as symptoms are often similar to those of other disorders, such as PD, PSP, and dementia with Lewy bodies, and a definitive diagnosis of CBS can only be made upon neuropathologic examination.

For the current study, the investigators recruited 26 patients with PD, 26 patients with either PSP (18) or CBS (8), and 26 healthy individuals (HC) from May 2014 to April 2017. All individuals underwent skin biopsy in three sites, the leg, the thigh, and the cervical area, to study p-syn deposits in skin nerves by immunofluorescence.

Results revealed that while all PD patients showed p-syn deposition, skin p-syn deposits were present in only two of the PSP/CBS patients and none of the HC. The two p-syn positive patients were diagnosed with PSP and CBS, respectively. These two patients were difficult to diagnose and could have a mixed pathology with multiple neurodegenerative disorders occurring at the same time.

“To our knowledge this is the largest study comparing in vivo the peripheral deposition of misfolded alpha-synuclein in PD and PSP/CBS cases,” said first author Dr. Maria Pia Giannoccaro, a researcher in the department of biomedical and neuromotor sciences at the University of Bologna (Italy). “We showed that the presence of skin p-syn deposits accurately distinguishes patients with PD from those with atypical parkinsonism. Early differentiation and accurate in vivo diagnosis are important for adequate clinical management and patient care since the treatment and prognosis of PD, PSP, and CBS are different.”

The study was published in the February 15, 2022, online edition of the Journal of Parkinson’s Disease.

Related Links:
University of Bologna

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