Contactin-1

Contactin-1 (CNTN1) is a cell adhesion molecule that mediates cell surface interactions critical for nervous system development (UniProt: Q12860). It functions in forming paranodal axo-glial junctions in myelinated peripheral nerves, facilitates signaling between axons and glial cells through interaction with CNTNAP1, and promotes oligodendrocyte generation by activating NOTCH1 signaling. The protein also modulates neurite outgrowth through interactions with TNR.

CNTN1 is expressed in neural tissues and has been associated with congenital myopathy 12 (CMYO12), an autosomal recessive disorder characterized by muscle weakness and sarcomeric disruption (UniProt: Q12860). Beyond this Mendelian condition, the protein's role in axonal-glial communication and myelin-related processes positions it within pathways relevant to neurodegeneration.

In Alzheimer's disease, CNTN1 is downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics, mean log2FC = −0.49), suggesting reduced levels across multiple subcellular fractions in TMT-labeled proteomic analysis. This downregulation may reflect compromise of axonal-glial integrity or myelin-associated processes in AD pathology.