Overlapping presence of β-amyloid, tau, p-tau, and α-synuclein in skin nerve fibers in Alzheimer's disease.

Abstract

Objective: Skin nerve fiber deposition of proteins can be strongly associated with neurodegenerative diseases, such as phosphorylated α-synuclein (p-SN) in synucleinopathies. Little is known about other neurodegenerative proteins, such as tau or β-amyloid, in skin nerve fibers of patients with Alzheimer's disease (AD) and their link to underlying neurodegeneration. We therefore aimed for describing the presence and distribution of these proteins in the skin of patients with AD and non-AD controls.

Methods: Skin biopsies were taken from 45 patients with AD (n = 23) and non-AD controls (n = 22). Nerve fibers were identified using antibodies against protein gene product 9.5 (PGP9.5), and protein deposits were evaluated with double-immunostaining of β-amyloid 1-42 (Aβ1-42), p-SN, tau, and phospho-tau (p-tau).

Results: Skin nerve fiber Aβ1-42 was present in 7/23 (30.4%) patients with AD and 7/22 (31.8%) controls. p-tau was detected in 12/23 (52.2%) patients with AD and 9/22 (40.9%) controls. Tau was present in 19/23 (82.6%) patients with AD and 16/22 (72.7%) controls. p-SN was detected in 12/23 (52.2%) patients with AD and 8/22 (36.4%) controls. Frequencies of deposits were not significantly different between groups and protein frequency did not correlate with severity of cognitive impairment.

Interpretation: Deposits of β-amyloid 1-42, p-SN, tau, and p-tau were detected in skin nerve fibers in both patient groups; however, qualitative assessment did not discriminate between AD and non-AD patients at this sample size. Future analyses of protein distribution and spreading in peripheral nerves may give new insights into the pathophysiology of neurodegenerative diseases, but may require quantitative detection.