Neuroinflammation in Alzheimer’s disease: Pleiotropic roles for cytokines and neuronal pentraxins

Swanson, Ashley; Wolf, Tovah; Sitzmann, Alli; Willette, Auriel A.

doi:10.1016/j.bbr.2018.02.015

Cited by 50 publications

(35 citation statements)

References 176 publications

(152 reference statements)

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“…Interestingly, both Neuronal pentraxin-1 (NPTX1) and Neuronal pentraxin receptor (NPTXR) showed consistent reduction (4 and 4 out of 5 studies, respectively). These proteins have been previously implicated in AD [47]. Although NPTX1 has been primarily considered as a plasma biomarker [48], the current analysis supports its role as a reliable CSF AD biomarker.…”

Section: Proteins Consistently Reduced In Ad Csfsupporting

confidence: 54%

A comprehensive systematic review of CSF proteins and peptides that define Alzheimer’s disease

et al. 2020

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Background: During the last two decades, over 100 proteomics studies have identified a variety of potential biomarkers in CSF of Alzheimer's (AD) patients. Although several reviews have proposed specific biomarkers, to date, the statistical relevance of these proteins has not been investigated and no peptidomic analyses have been generated on the basis of specific up-or down-regulation. Herein, we perform an analysis of all unbiased explorative proteomics studies of CSF biomarkers in AD to critically evaluate whether proteins and peptides identified in each study are consistent in distribution; direction change; and significance, which would strengthen their potential use in studies of AD pathology and progression. Methods: We generated a database containing all CSF proteins whose levels are known to be significantly altered in human AD from 47 independent, validated, proteomics studies. Using this database, which contains 2022 AD and 2562 control human samples, we examined whether each protein is consistently present on the basis of reliable statistical studies; and if so, whether it is over-or under-represented in AD. Additionally, we performed a direct analysis of available mass spectrometric data of these proteins to generate an AD CSF peptide database with 3221 peptides for further analysis. Results: Of the 162 proteins that were identified in 2 or more studies, we investigated their enrichment or depletion in AD CSF. This allowed us to identify 23 proteins which were increased and 50 proteins which were decreased in AD, some of which have never been revealed as consistent AD biomarkers (i.e. SPRC or MUC18). Regarding the analysis of the tryptic peptide database, we identified 87 peptides corresponding to 13 proteins as the most highly consistently altered peptides in AD. Analysis of tryptic peptide fingerprinting revealed specific peptides encoded by CH3L1, VGF, SCG2, PCSK1N, FBLN3 and APOC2 with the highest probability of detection in AD. Conclusions: Our study reveals a panel of 27 proteins and 21 peptides highly altered in AD with consistent statistical significance; this panel constitutes a potent tool for the classification and diagnosis of AD.

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Section: Proteins Consistently Reduced In Ad Csfsupporting

confidence: 54%

A comprehensive systematic review of CSF proteins and peptides that define Alzheimer’s disease

et al. 2020

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“…Although their functions are not well understood, it is hypothesized that chitinases are involved in pro-inflammatory and proangiogenic tissue remodeling in cancer [23,24] as well as in several neurodegenerative diseases [25][26][27][28][29][30][31][32]. CHI3L1 found in the cerebral spinal fluid (CSF) obtained from preclinical and prodromal cases of AD [33][34][35] has been suggested as a biomarker for discerning cognitively normal from mild cognitive impairment (MCI) individuals [25,36,37]. Human tissue-based studies revealed that CHI3L1 is expressed in astrocytes in close apposition to blood vessels, Aβ plaques and NFTs in AD [38].…”

Section: Introductionmentioning

confidence: 99%

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

Moreno‐Rodríguez

Perez

Nadeem

et al. 2020

J Neuroinflammation

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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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“…The nervous system includes the central nervous system and the peripheral nervous system. A large number of studies have found that the occurrence of various neurological diseases is closely related to neuroinflammation, which is caused by infections, trauma, toxic metabolites, and autoimmune abnormalities (75)(76)(77). Previous research suggested that circRNAs are widely distributed in the mammalian brain, at even higher abundance than the abundance of corresponding linear transcripts (7).…”

Section: Circrnas In the Neurological Diseasesmentioning

confidence: 99%

The Role of Circular RNAs in Immune-Related Diseases

Xie

Zhang

et al. 2020

Front. Immunol.

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Circular RNAs (circRNAs) are a novel class of RNAs with a covalently closed loop structure without a 3 ′ polyadenylation [poly-(A)] tail or a 5 ′ cap. They used to be considered as the occasional and useless products of RNA splicing errors because they could not be detected by traditional RNA sequencing technology. Benefiting from the development of specific biochemical and computational approaches, researchers showed that circRNAs are universally expressed and functional. Further studies have revealed their important functions regarding regulating gene expression at the transcriptional and post-transcriptional levels. These functions include acting as microRNA (miRNA) sponges, binding to RNA-binding proteins (RBPs), acting as transcriptional regulatory factors, and serving as translation templates. The advances in circRNA research has opened researchers' eyes to a new area of research on the roles of circRNAs in the pathogenesis of various diseases, especially at the immune level because of the close relationship between circRNAs and the immune response. Emerging research indicates that circRNAs could act as potential biomarkers related to diagnosis, therapeutic effects, and prognosis, and they may be effective therapeutic targets in immunological disorders, including certain diseases that are currently difficult to treat.

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Neuroinflammation in Alzheimer’s disease: Pleiotropic roles for cytokines and neuronal pentraxins

Cited by 50 publications

References 176 publications

A comprehensive systematic review of CSF proteins and peptides that define Alzheimer’s disease

A comprehensive systematic review of CSF proteins and peptides that define Alzheimer’s disease

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

The Role of Circular RNAs in Immune-Related Diseases

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