Parkinson’s biomarker could be only skin deep

By Eleanor McDermid, Senior medwireNews Reporter

Deposits of α-synuclein in cutaneous nerves could represent a noninvasive biomarker for Parkinson’s disease (PD), say researchers.

Abnormal α-synuclein deposits have been reported in other parts of the peripheral nervous system, such as the olfactory nerves, vagus nerve, and colonic submucosal plexus, but unlike these, the skin is simple and noninvasive to biopsy.

Using fluorescent microscopy, Roy Freeman (Harvard Medical School, Boston, Massachusetts, USA) and team detected α-synuclein in skin biopsies of all 20 PD patients (average disease duration of 4.2 years) and 14 age- and gender-matched controls who participated in the study.

Previous studies using a similar approach did not detect α-synuclein in all participants. Freeman et al attribute this largely to previous researchers’ use of antibodies to phosphorylated α-synuclein, whereas they used a more general α-synuclein antibody.

As reported in Neurology, the team detected α-synuclein in autonomic fibers in the dermal layer, but not in nociceptive sensory fibers. Although all participants had some α-synuclein present, PD patients had a significantly higher ratio of α-synuclein to nerve fiber density than controls, at about 0.8 versus 0.2 for the pilomotor (adrenergic) fibers and about 0.3 versus less than 0.05 for the sudomotor (sympathetic cholinergic) fibers.

This pattern was consistent for the three sites biopsied: the distal leg; distal thigh; and proximal thigh.

PD patients had reduced pilomotor fiber density relative to controls, and this correlated with higher α-synuclein ratios. Sudomotor nerve density was similar in patients and controls, yet higher α-synuclein ratios still correlated with lower nerve density in the patients.

Increased α-synuclein ratios in PD patients also correlated with autonomic dysfunction and higher Hoehn and Yahr scores.

In an accompanying editorial, William Cheshire (Mayo Clinic, Jacksonville, Florida, USA) and Ronald Pfeiffer (University of Tennessee Health Science Center, Memphis, USA) say: “These findings hold promise that further clues to a deeper understanding of the molecular and neuronal pathology of PD may be accessible just beneath the body's surface where affected autonomic nerves innervate cutaneous structures.”

However, they caution that “[c]linical use of skin biopsies to diagnose or stage PD would be premature at this time.”

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