CCL2 Is Associated with a Faster Rate of Cognitive Decline during Early Stages of Alzheimer's Disease.
Westin, Karin ; Buchhave, Peder LU ; Nielsen, Henrietta LU ; Minthon, Lennart LU ; Janciauskiene, Sabina LU and Hansson, Oskar LU
(2012)
In PLoS ONE
7(1).
- Abstract
- Chemokine (C-C motif) receptor 2 (CCR2)-signaling can mediate accumulation of microglia at sites affected by neuroinflammation. CCR2 and its main ligand CCL2 (MCP-1) might also be involved in the altered metabolism of beta-amyloid (Aβ) underlying Alzheimer's disease (AD). We therefore measured the levels of CCL2 and three other CCR2 ligands, i.e. CCL11 (eotaxin), CCL13 (MCP-4) and CCL26 (eotaxin-3), in the cerebrospinal fluid (CSF) and plasma of 30 controls and 119 patients with mild cognitive impairment (MCI) at baseline. During clinical follow-up 52 MCI patients were clinically stable for five years, 47 developed AD (i.e. cases with prodromal AD at baseline) and 20 developed other dementias. Only CSF CCL26 was statistically significantly... (More)
- Chemokine (C-C motif) receptor 2 (CCR2)-signaling can mediate accumulation of microglia at sites affected by neuroinflammation. CCR2 and its main ligand CCL2 (MCP-1) might also be involved in the altered metabolism of beta-amyloid (Aβ) underlying Alzheimer's disease (AD). We therefore measured the levels of CCL2 and three other CCR2 ligands, i.e. CCL11 (eotaxin), CCL13 (MCP-4) and CCL26 (eotaxin-3), in the cerebrospinal fluid (CSF) and plasma of 30 controls and 119 patients with mild cognitive impairment (MCI) at baseline. During clinical follow-up 52 MCI patients were clinically stable for five years, 47 developed AD (i.e. cases with prodromal AD at baseline) and 20 developed other dementias. Only CSF CCL26 was statistically significantly elevated in patients with prodromal AD when compared to controls (p = 0.002). However, in patients with prodromal AD, the CCL2 levels in CSF at baseline correlated with a faster cognitive decline during follow-up (r(s) = 0.42, p = 0.004). Furthermore, prodromal AD patients in the highest tertile of CSF CCL2 exhibited a significantly faster cognitive decline (p<0.001) and developed AD dementia within a shorter time period (p<0.003) compared to those in the lowest tertile. Finally, in the entire MCI cohort, CSF CCL2 could be combined with CSF Tau, P-tau and Aβ42 to predict both future conversion to AD and the rate of cognitive decline. If these results are corroborated in future studies, CCL2 in CSF could be a candidate biomarker for prediction of future disease progression rate in prodromal AD. Moreover, CCR2-related signaling pathways might be new therapeutic targets for therapies aiming at slowing down the disease progression rate of AD. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2367319
- author
- Westin, Karin
; Buchhave, Peder
LU
; Nielsen, Henrietta
LU
; Minthon, Lennart
LU
; Janciauskiene, Sabina
LU
and Hansson, Oskar
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 7
- issue
- 1
- article number
- e30525
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000301770300002
- pmid:22303443
- scopus:84856383137
- pmid:22303443
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0030525
- language
- English
- LU publication?
- yes
- id
- cab23744-f86a-4ade-90f2-8c2cf693d91a (old id 2367319)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22303443?dopt=Abstract
- date added to LUP
- 2016-04-01 13:42:46
- date last changed
- 2022-05-19 20:44:45
@article{cab23744-f86a-4ade-90f2-8c2cf693d91a,
abstract = {{Chemokine (C-C motif) receptor 2 (CCR2)-signaling can mediate accumulation of microglia at sites affected by neuroinflammation. CCR2 and its main ligand CCL2 (MCP-1) might also be involved in the altered metabolism of beta-amyloid (Aβ) underlying Alzheimer's disease (AD). We therefore measured the levels of CCL2 and three other CCR2 ligands, i.e. CCL11 (eotaxin), CCL13 (MCP-4) and CCL26 (eotaxin-3), in the cerebrospinal fluid (CSF) and plasma of 30 controls and 119 patients with mild cognitive impairment (MCI) at baseline. During clinical follow-up 52 MCI patients were clinically stable for five years, 47 developed AD (i.e. cases with prodromal AD at baseline) and 20 developed other dementias. Only CSF CCL26 was statistically significantly elevated in patients with prodromal AD when compared to controls (p = 0.002). However, in patients with prodromal AD, the CCL2 levels in CSF at baseline correlated with a faster cognitive decline during follow-up (r(s) = 0.42, p = 0.004). Furthermore, prodromal AD patients in the highest tertile of CSF CCL2 exhibited a significantly faster cognitive decline (p<0.001) and developed AD dementia within a shorter time period (p<0.003) compared to those in the lowest tertile. Finally, in the entire MCI cohort, CSF CCL2 could be combined with CSF Tau, P-tau and Aβ42 to predict both future conversion to AD and the rate of cognitive decline. If these results are corroborated in future studies, CCL2 in CSF could be a candidate biomarker for prediction of future disease progression rate in prodromal AD. Moreover, CCR2-related signaling pathways might be new therapeutic targets for therapies aiming at slowing down the disease progression rate of AD.}},
author = {{Westin, Karin and Buchhave, Peder and Nielsen, Henrietta and Minthon, Lennart and Janciauskiene, Sabina and Hansson, Oskar}},
issn = {{1932-6203}},
language = {{eng}},
number = {{1}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{CCL2 Is Associated with a Faster Rate of Cognitive Decline during Early Stages of Alzheimer's Disease.}},
url = {{https://lup.lub.lu.se/search/files/3545054/2544327.pdf}},
doi = {{10.1371/journal.pone.0030525}},
volume = {{7}},
year = {{2012}},
}