Brain CHID1 Expression Correlates with NRGN and CALB1 in Healthy Subjects and AD Patients.

Paola Castrogiovanni,Rosa Imbesi,Giuseppe Musumeci,Grazia Maugeri,Cristina Sanfilippo,Michelino Di Rosa,Alessandro Castorina,Daniele Tibullo,Debora Lo Furno

doi:10.3390/cells10040882

Paola Castrogiovanni, Rosa Imbesi + Show 7 more

Open Access

https://doi.org/10.3390/cells10040882

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Abstract

Alzheimer’s disease is a progressive, devastating, and irreversible brain disorder that, day by day, destroys memory skills and social behavior. Despite this, the number of known genes suitable for discriminating between AD patients is insufficient. Among the genes potentially involved in the development of AD, there are the chitinase-like proteins (CLPs) CHI3L1, CHI3L2, and CHID1. The genes of the first two have been extensively investigated while, on the contrary, little information is available on CHID1. In this manuscript, we conducted transcriptome meta-analysis on an extensive sample of brains of healthy control subjects (n = 1849) (NDHC) and brains of AD patients (n = 1170) in order to demonstrate CHID1 involvement. Our analysis revealed an inverse correlation between the brain CHID1 expression levels and the age of NDHC subjects. Significant differences were highlighted comparing CHID1 expression of NDHC subjects and AD patients. Exclusive in AD patients, the CHID1 expression levels were correlated positively to calcium-binding adapter molecule 1 (IBA1) levels. Furthermore, both in NDHC and in AD patient’s brains, the CHID1 expression levels were directly correlated with calbindin 1 (CALB1) and neurogranin (NRGN). According to brain regions, correlation differences were shown between the expression levels of CHID1 in prefrontal, frontal, occipital, cerebellum, temporal, and limbic system. Sex-related differences were only highlighted in NDHC. CHID1 represents a new chitinase potentially involved in the principal processes underlying Alzheimer’s disease.

Highlights

Neurodegeneration indicates a progressive structural, functional, and molecular alteration of neurons, with consequent progressive cell degeneration
A total of 1853 data points from frozen tissue samples were selected belonging to subjects who did not die from causes related to neurological diseases that we have identified as non-demented healthy controls subjects (NDHC) (70.63 ± 12.45 years) and 1170 samples taken from Alzheimer’s disease (AD) patients (82.03 ± 9.29 years)
Brain CHID1 RNA expression levels were significantly lower in patients with AD as compared to NDHC subjects (Figure 1A,B)

Summary

Introduction

Neurodegeneration indicates a progressive structural, functional, and molecular alteration of neurons, with consequent progressive cell degeneration. The molecular mechanisms that regulate these diseases are present in aging and neurodegenerative diseases. Being able to understand the principal molecules that regulate the cellular mechanisms of the neuroglia represents a new strategy to counteract the development and progression of neurodegenerative diseases. The accumulation of Aβ peptides results in neuron death and local immune activation, which leads to synaptic and cognitive dysfunctions. Several proteins, such as chitinases [6], calcium-binding adapter molecule 1 (IBA1) [7], platelet endothelial cell adhesion molecule (CD31) [8], and calbindin 1 (CALB1) [9], could be considered new potential markers of the cellular architecture alteration of the nervous system parenchyma

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