Contactin-associated protein 1

Contactin-associated protein 1 (CNTNAP1, also known as Caspr) is a 1384-amino acid protein essential for organizing myelinated axons and maintaining the paranodal region at the axo-glial junction (UniProt: P78357). Working in association with contactin and CNTNAP2, it organizes the radial and longitudinal structure of myelin and facilitates saltatory conduction of nerve impulses through signaling between axons and myelinating glial cells.

CNTNAP1 mutations cause severe neurological developmental disorders, including lethal congenital contracture syndrome 7 (LCCS7; MIM 616286) and congenital hypomyelinating neuropathy 3 (CHN3; MIM 618186), both characterized by profound deficits in myelination, motor development, and axo-glial structure (UniProt: P78357).

In Alzheimer's disease, CNTNAP1 is significantly downregulated in post-mortem AD brain compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.33 across analyzed subcellular fractions. This downregulation may reflect compromised axonal organization and myelin integrity, processes increasingly recognized as relevant to neurodegeneration in AD.