Contactin 5 and Apolipoproteins Interplay in Alzheimer's Disease

J Alzheimers Dis. 2024;98(4):1361-1375. doi: 10.3233/JAD-231003.


Background: 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.

Keywords: Alzheimer’s disease; CNTN5; apolipoprotein B; apolipoprotein D; apolipoprotein E; apolipoprotein J; apolipoproteins; contactin 5; contactins; gene expression.

MeSH terms

  • Alzheimer Disease* / metabolism
  • Animals
  • Apolipoproteins / genetics
  • Apolipoproteins B
  • Apolipoproteins E / metabolism
  • Cholesterol
  • Contactins
  • Humans
  • Mice


  • Apolipoproteins
  • Apolipoproteins E
  • Apolipoproteins B
  • Cholesterol
  • Contactins