Contactin 5 and Apolipoproteins Interplay in Alzheimer’s Disease (Dauar MT et al., 2024)

Citation :
Dauar, M. T., Picard, C., Labonté, A., Breitner, J., Rosa-Neto, P., Villeneuve, S., Poirier, J., & PREVENT-AD Research Group (2024). Contactin 5 and Apolipoproteins Interplay in Alzheimer’s Disease. Journal of Alzheimer’s disease : JAD98(4), 1361–1375.

Full text : Here

Dauar, MT, Picard C, Labonté A, Breitner J, Rosa-Neto P, Villeneuve S, Poirier J & PREVENT-AD Research Group

published in Journal of Alzheimer’s Disease, April 2024.

Apolipoproteins and contactin 5 are proteins associated with Alzheimer’s disease (AD) pathophysiology. Apolipoproteins act on transport and clearance of cholesterol and phospholipids during synaptic turnover and terminal proliferation. Contactin 5 is a neuronal membrane protein involved in key processes of neurodevelopment. Objective:To investigate the interactions between contactin 5 and apolipoproteins in AD, and the role of these proteins in response to neuronal damage. Methods:Apolipoproteins (measured by Luminex), contactin 5 (measured by Olink’s proximity extension assay), and cholesterol (measured by liquid chromatography mass spectrometry) were assessed in the cerebrospinal fluid (CSF) and plasma of cognitively unimpaired participants (n = 93). Gene expression was measured using polymerase chain reaction in the frontal cortex of autopsied-confirmed AD (n = 57) and control subjects (n = 31) and in the hippocampi of mice following entorhinal cortex lesions. Results: Contactin 5 positively correlated with apolipoproteins B (p = 5.4×10–8), D (p = 1.86×10–4), E (p = 2.92×10–9), J (p = 2.65×10–9), and with cholesterol (p = 0.0096) in the CSF, and with cholesterol (p = 0.02), HDL (p = 0.0143), and LDL (p = 0.0121) in the plasma. Negative correlations were seen between CNTN5, APOB (p = 0.034) and APOE (p = 0.015) mRNA levels in the brains of control subjects. In the mouse model, apoe and apoj gene expression increased during the reinnervation phase (p <  0.05), while apob (p = 0.023) and apod (p = 0.006) increased in the deafferentation stage. Conclusions: Extensive interactions were observed between contactin 5 and apolipoproteins and cholesterol, possibly due to neuronal damage. The alterations in gene expression of apolipoproteins suggest a role in axonal, terminal, and synaptic remodeling in response to entorhinal cortex damage.