Contactin 5 and Apolipoproteins Interplay in Alzheimer's Disease.
J Alzheimers Dis
; 98(4): 1361-1375, 2024.
Article
em En
| MEDLINE
| ID: mdl-38578887
ABSTRACT
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 (nâ=â93). Gene expression was measured using polymerase chain reaction in the frontal cortex of autopsied-confirmed AD (nâ=â57) and control subjects (nâ=â31) and in the hippocampi of mice following entorhinal cortex lesions.Results:
Contactin 5 positively correlated with apolipoproteins B (pâ=â5.4×10-8), D (pâ=â1.86×10-4), E (pâ=â2.92×10-9), J (pâ=â2.65×10-9), and with cholesterol (pâ=â0.0096) in the CSF, and with cholesterol (pâ=â0.02), HDL (pâ=â0.0143), and LDL (pâ=â0.0121) in the plasma. Negative correlations were seen between CNTN5, APOB (pâ=â0.034) and APOE (pâ=â0.015) mRNA levels in the brains of control subjects. In the mouse model, apoe and apoj gene expression increased during the reinnervation phase (pâ< â0.05), while apob (pâ=â0.023) and apod (pâ=â0.006) 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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Alzheimers Dis
Assunto da revista:
GERIATRIA
/
NEUROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Canadá