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Published in: Journal of Neuroinflammation 1/2020

01-12-2020 | Alzheimer's Disease | Research

Frontal cortex chitinase and pentraxin neuroinflammatory alterations during the progression of Alzheimer’s disease

Authors: Marta Moreno-Rodriguez, Sylvia E. Perez, Muhammad Nadeem, Michael Malek-Ahmadi, Elliott J. Mufson

Published in: Journal of Neuroinflammation | Issue 1/2020

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Abstract

Background

Chitinase 3-like 1 (CHI3L1), chitinase 3-like 2 (CHI3L2), and neuronal pentraxin II (NPTX2) are inflammatory biomarkers of Alzheimer’s disease (AD). Although studies have demonstrated that cerebrospinal fluid levels of these proteins are changed in AD, no studies have undertaken a detailed examination of alterations in protein levels, cellular expression, and interaction with amyloid in the brain during the progression of AD.

Methods

The study evaluated levels of both CHI3L1 and CHI3L2, NPTX2, ionized calcium-binding adapter molecule 1 (Iba1), complement component 1q (C1q), glial fibrillary acidic protein (GFAP), and CD44, in the frontal cortex of people who died with an antemortem clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), mild/moderate AD (mAD), and severe AD (sAD) using immunoblot and immunohistochemical techniques.

Results

CHI3L1-immunoreactive (-ir) astrocyte numbers were increased in the frontal cortex and white matter in sAD compared to NCI. On the other hand, increases in GFAP and Iba1-ir cell numbers were observed in MCI compared to NCI but only in white matter. Western blot analyses revealed significantly lower frontal cortex CHI3L2 levels, whereas CD44 levels were increased in sAD. No significant differences for CHI3L1, GFAP, C1q, and NPTX2 protein levels were detected between clinical groups. Strong significant correlations were found between frontal cortex CHI3L1 and Iba1-ir cell numbers in white matter and CHI3L1 and C1q protein levels in the early stages of the disease. C1q and Iba1, CD44 with CHI3L2, and GFAP protein levels were associated during disease progression. CHI3L1 and Iba1 cell numbers in white matter showed a significant associations with episodic memory and perceptual speed.

Conclusions

White matter CHI3L1 inflammatory response is associated with cognitive impairment early in the onset of AD.
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Metadata
Title
Frontal cortex chitinase and pentraxin neuroinflammatory alterations during the progression of Alzheimer’s disease
Authors
Marta Moreno-Rodriguez
Sylvia E. Perez
Muhammad Nadeem
Michael Malek-Ahmadi
Elliott J. Mufson
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2020
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-020-1723-x

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