Skin nerve phosphorylated α-synuclein in the elderly

Area of Science:

• Neurology
• Pathology
• Gerontology

Background:

• Phosphorylated alpha-synuclein (p-syn) is a hallmark of synucleinopathies like Parkinson's disease.
• Incidental Lewy bodies are common in elderly individuals, but their clinical significance is unclear.
• Small fiber neuropathy can be an early sign of synucleinopathies.

Purpose of the Study:

• To determine the incidence of p-syn in skin nerves of very old, healthy subjects.
• To evaluate skin biopsy as a diagnostic tool for synucleinopathies in vivo.

Main Methods:

• Prospective skin biopsies were performed on 33 elderly subjects (>70 years).
• Subjects underwent neurological examination.
• Literature review of PubMed publications (2013-2023) on skin p-syn in healthy controls.

Main Results:

• p-syn was not detected in the skin nerves of 31 healthy subjects.
• Two very elderly subjects (>98 years) with neurological signs of extrapyramidal disorder showed p-syn.
• Literature search revealed p-syn in only 4 out of 490 healthy subjects tested.

Conclusions:

• p-syn is virtually absent in the skin nerves of healthy individuals, including the very elderly.
• Skin biopsy is a highly specific diagnostic tool for identifying synucleinopathies in vivo.
• The presence of p-syn in skin nerves may indicate an underlying synucleinopathy even in the absence of overt clinical symptoms.