Characterization of the contactin 5 protein and its risk-associated polymorphic variant throughout the Alzheimer's disease spectrum

Introduction: We investigate the CNTN5 rs1461684 G variant and the contactin 5 protein in sporadic Alzheimer's disease (sAD).

Methods: Contactin 5, sAD biomarkers, and synaptic markers were measured in the cerebrospinal fluid (CSF). Amyloid and tau deposition were assessed using positron emission tomography. Contactin 5 protein and mRNA levels were measured in brain tissue.

Results: CSF contactin 5 increases progressively in cognitively unimpaired individuals and is decreased in mild cognitive impairment and sAD. CSF contactin 5 correlates with sAD biomarkers and with synaptic markers. The rs1461684 G variant associates with faster disease progression in cognitively unimpaired subjects. Cortical full-length and isoform 3 CNTN5 mRNAs are decreased in the presence of the G allele and as a function of Consortium to Establish a Registry for Alzheimer's Disease stages.

Discussion: The newly identified rs1461684 G variant associates with sAD risk, rate of disease progression, and gene expression. Contactin 5 protein and mRNA are affected particularly in the early stages of the disease.