TY - JOUR
T1 - Postsynaptic damage and microglial activation in AD patients could be linked CXCR4/CXCL12 expression levels
AU - Sanfilippo, Cristina
AU - Castrogiovanni, Paola
AU - Imbesi, Rosa
AU - Nunnari, Giuseppe
AU - Di Rosa, Michelino
N1 - Funding Information:
We would like to show our gratitude to the authors of microarray datasets made available online, for consultation and re-analysis. In addition, I would like to express my gratitude to Oliver Di Rosa, an inspiration in my life. This article does not contain any studies with human participants or animals performed by any of the authors.
Publisher Copyright:
© 2020 Elsevier B.V.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/15
Y1 - 2020/12/15
N2 - Alzheimer's disease (AD) is one of the most common forms of dementia with still unknown pathogenesis. Several cytokines and chemokines are involved in the pathogenesis of AD. Among the chemokines, the CXCR4/CXCL12 complex has been shown to play an important role in the pathogenetic development of AD. We investigated the expression levels of CXCR4 / CXCL12 in fifteen brain regions of healthy non-demented subjects (NDHC) (2139 sample) and AD patients (1170 sample) stratified according to sex and age. Furthermore, we correlated their expressions with the Neurogranin (NRGN) and CHI3L1 levels, two inflamm-aging markers. We highlighted that CXCR4 gene expression levels were age-correlated in the brain of NDHC subjects and that AD nullified this correlation. A similar trend, but diametrically opposite was observed for CXCL12. Its expression was decreased during the aging in both sexes, and in the brains of AD patients, it underwent an inversion of the trend, only and exclusively in females. Brains of AD patients expressed high CXCR4 and CHI3L1, and low CXCL12 and Neurogranin levels compared to NDHC subjects. Both CXCR4 and CXCL12 correlated significantly with CHI3L1 and Neurogranin expression levels, regardless of disease. Furthermore, we showed a selective modulation of CXCL12 and CXCR4 only in specific brain regions. Taken together our results demonstrate that CXCL12 and CXCR4 are linked to Neurogranin and CHI3L1 expression levels and the relationship between postsynaptic damage and microglial activation in AD could be shown using all these genes. Further confirmations are needed to demonstrate the close link between these genes.
AB - Alzheimer's disease (AD) is one of the most common forms of dementia with still unknown pathogenesis. Several cytokines and chemokines are involved in the pathogenesis of AD. Among the chemokines, the CXCR4/CXCL12 complex has been shown to play an important role in the pathogenetic development of AD. We investigated the expression levels of CXCR4 / CXCL12 in fifteen brain regions of healthy non-demented subjects (NDHC) (2139 sample) and AD patients (1170 sample) stratified according to sex and age. Furthermore, we correlated their expressions with the Neurogranin (NRGN) and CHI3L1 levels, two inflamm-aging markers. We highlighted that CXCR4 gene expression levels were age-correlated in the brain of NDHC subjects and that AD nullified this correlation. A similar trend, but diametrically opposite was observed for CXCL12. Its expression was decreased during the aging in both sexes, and in the brains of AD patients, it underwent an inversion of the trend, only and exclusively in females. Brains of AD patients expressed high CXCR4 and CHI3L1, and low CXCL12 and Neurogranin levels compared to NDHC subjects. Both CXCR4 and CXCL12 correlated significantly with CHI3L1 and Neurogranin expression levels, regardless of disease. Furthermore, we showed a selective modulation of CXCL12 and CXCR4 only in specific brain regions. Taken together our results demonstrate that CXCL12 and CXCR4 are linked to Neurogranin and CHI3L1 expression levels and the relationship between postsynaptic damage and microglial activation in AD could be shown using all these genes. Further confirmations are needed to demonstrate the close link between these genes.
KW - Aging
KW - Alzheimer's disease
KW - Bioinformatics
KW - CHI3L1
KW - Chitinase
KW - NRGN
UR - http://www.scopus.com/inward/record.url?scp=85091491891&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85091491891&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2020.147127
DO - 10.1016/j.brainres.2020.147127
M3 - Article
C2 - 32949560
AN - SCOPUS:85091491891
VL - 1749
SP - 1
EP - 13
JO - Brain Research
JF - Brain Research
SN - 0006-8993
M1 - 147127
ER -