2026 American Academy of Neurology Abstract Website

Objective:

To investigate whether skin-derived proteins can serve as potential biomarkers in people with Parkinson's Disease (PwP)

Background:

Skin and brain originate from the embryonic ectoderm and share common molecular pathways. Parkinson’s disease (PD) is associated with seborrheic dermatitis, altered sweating, and increased melanoma risk. We examined whether skin tape-strip sampling and skin biopsy can generate biomarker proteomic signatures in people with PD (PwP).

Design/Methods:

We collected samples from Irish PwP by tape-stripping from forehead (n=71; M=54, F=17) and upper back skin biopsy (n=65; M=50, F=15), and compared to neurologically-healthy controls (HC, tape-strip n=74; M=53, F=21 and biopsy n=67, M=47, F=20). Proteins were analysed by high-resolution LC-MS/MS, with data processed in MaxQuant for peptide ID and label-free quantification. Filtered protein outputs were annotated and used in pathway analysis.

Results:

Skin tape-strip: Seventeen proteins were upregulated and 80 downregulated at p<0.05 in PwP versus HC, including several previously reported in plasma or other PD proteomic studies. Proteins not previously reported included LCN2, CHI3L2, CRABP2, CA2,MAN2B1, SERPINB3, NCCRP1, RNASE7 etc (upregulated) and A2M, HP, FGA, TF, KRT3, CP, KRT31, CUTA, APOA2, KRT86;KRT81, KRT85, APOB, HBA1, HBB, LACRT etc. (downregulated).

Skin biopsy: Forty-six proteins were upregulated, and 85 proteins downregulated at p<0.05 in PwP versus HC, including several previously reported in other proteomic PD studies. Proteins not previously reported included EIF3I,ATP5J2,EPPK1,FLG2,PDHB,ALDH9A1,PYCARD etc. (upregulated) and MDH1, YWHAZ, LUM, DPYSL2, IGLC6, DCN, SOD3, ITIH2, GNB1, TPM1, TNXB, HSP90B1, ABI3BP, APOA2, COL6A3, IGLL5;IGLC1 etc. (downregulated).

KEGG, Enricher pathway analysis revealed strong signatures in both that relate to lipid metabolism, immunity, apoptosis and keratin formation.

Conclusions:

We identified a range of alterations in the skin-associated proteome of PwP compared to healthy controls, some of which may serve as clinical or pathologic biomarkers.