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

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.

Broad transcriptional dysregulation of brain and choroid plexus cell types with COVID-19

“…Given SARS-CoV-2 infection of barrier cells, we thus wondered whether astrocytes would exhibit similar hallmarks of inflammation with concomitant consequences for neuronal health. We indeed observed hallmarks of astrogliosis 87 and viral defense 50 in upregulated GFAP and IFITM3 expression, as well as neurotoxicity in the secreted factor CHI3L1 88–90 (Fig. 3b, Fig.…”

Systematic review of human post‐mortem immunohistochemical studies and bioinformatics analyses unveil the complexity of astrocyte reaction in Alzheimer's disease

“…In addition, some studies have shown increased immunoreactivity for transcription factors known to mediate immune and inflammatory responses such as nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2) [ 54 ]; nuclear factor of activated T-cells, cytoplasmic 4 (NFATC4) [ 54 ]; transcription factor p65 (RELA, also known as nuclear factor NF-kappa-B p65 subunit) [ 55 , 56 ]; adipocyte enhancer-binding protein 1 (AEBP1) [ 57 ]; CCAAT/enhancer-binding protein delta (CEBPD) [ 58 ]; and glia maturation factor (e.g., GMFB) [ 59 , 60 ]. Lastly, reactive astrocytes also express chitinase-3-like protein 1 (CHI3L1, also known as YKL-40) [ 61 – 64 ] and the 18 kDa translocator protein (TSPO) [ 65 , 66 ]; although their function remains to be fully elucidated, these two proteins are commonly interpreted as evidence of inflammation when measured in CSF and detected via PET imaging, respectively.…”

Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer’s Disease Patients

“…Among them, we found hsa-miR-671-5p and Thrombospondin 1 (THBS1), an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein can bind to fibrinogen, fibronectin, laminin, type V collagen, and integrins alpha-V/beta-1, hsa-miR-132-3p, and hsa-miR-212-3p, inversely related to CD44, which was previously found upregulated in severe Alzheimer’s disease [ 46 ]. hsa-miR-30e-5p and Integrin beta-1 (ITGB1), a receptor for collagen, is another interaction, and it was suggested to undergo plasticity through interactions with ECM proteins, modulating ion channels, intracellular Ca 2+ and protein kinases signalling, and reorganization of cytoskeletal filaments [ 47 ].…”