A sex-stratified analysis of neuroimmune gene expression signatures in Alzheimer's disease brains
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F23%3A00079785" target="_blank" >RIV/00159816:_____/23:00079785 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s11357-022-00664-7" target="_blank" >https://link.springer.com/article/10.1007/s11357-022-00664-7</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s11357-022-00664-7" target="_blank" >10.1007/s11357-022-00664-7</a>
Alternative languages
Result language
angličtina
Original language name
A sex-stratified analysis of neuroimmune gene expression signatures in Alzheimer's disease brains
Original language description
Alzheimer's disease (AD) is the most common form of progressively disabling dementia. The chitinases CHI3L1 and CHI3L2 have long been known as biomarkers for microglial and astrocytic activation in neurodegeneration. Here, we collected microarray datasets from the National Center for Biotechnology Information (NCBI) brain samples of non-demented controls (NDC) (n = 460), and of deceased patients with AD (n = 697). The AD patients were stratified according to sex. Comparing the high CHI3L1 and CHI3L2 expression group (75(th) percentile), and low CHI3L1 and CHI3L2 expression group (25(th) percentile), we obtained eight signatures according to the sex of patients and performed a genomic deconvolution analysis using neuroimmune signatures (NIS) belonging to twelve cell populations. Expression analysis revealed significantly higher CHI3L1 and CHI3L2 expression in AD compared with NDC, and positive correlations of these genes with GFAP and TMEM119. Furthermore, deconvolution analysis revealed that CHI3L1 and CHI3L2 high expression was associated with inflammatory signatures in both sexes. Neuronal activation profiles were significantly activated in AD patients with low CHI3L1 and CHI3L2 expression levels. Furthermore, gene ontology analysis of common genes regulated by the two chitinases unveiled immune response as a main biological process. Finally, microglia NIS significantly correlated with CHI3L2 expression levels and were more than 98% similar to microglia NIS determined by CHI3L1. According to our results, high levels of CHI3L1 and CHI3L2 in the brains of AD patients are associated with inflammatory transcriptomic signatures. The high correlation between CHI3L1 and CHI3L2 suggests strong co-regulation.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30227 - Geriatrics and gerontology
Result continuities
Project
<a href="/en/project/EF15_003%2F0000492" target="_blank" >EF15_003/0000492: Unveiling the molecular determinants of agingto design new therapeutics</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
GeroScience
ISSN
2509-2715
e-ISSN
2509-2723
Volume of the periodical
45
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
19
Pages from-to
523-541
UT code for WoS article
000856603400002
EID of the result in the Scopus database
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