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Cited by 279Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

The DOI matches its Crossref record; 27 of the 28 references it cites were found in a registry or an index.

CCL2 Is Associated with a Faster Rate of Cognitive Decline during Early Stages of Alzheimer's Disease

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Westin, Karin, Buchhave, Peder, Nielsen, Henrietta, Minthon, Lennart, Janciauskiene, Sabina, Hansson, Oskar·2012·PLoS ONE
DOI 10.1371/journal.pone.0030525PMC PMC3268759
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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.

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Crossref · 10.1371/journal.pone.0030525

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Figure 1 The baseline levels of CCL2 in the cerebrospinal fluid correlated positively with the annual change in MMSE score during clinical follow-up (r s = 0.42, p = 0.004).
Figure 1 The baseline levels of CCL2 in the cerebrospinal fluid correlated positively with the annual change in MMSE score during clinical follow-up (r s = 0.42, p = 0.004).CC BY · PubMed Central
Figure 2 The disease progression rate is increased in cases with prodromal AD who have higher levels of CCL2 in the cerebrospinal fluid at baseline. Panel A shows that prodromal AD cases in the highest tertile of CSF CCL2 at baseline exhibited a significantly higher annual decrease in MMSE score during the follow-up period compared to those in the lowest tertile (p<0.001, Mann Whitney U test). Panel B depicts that prodromal AD cases in the highest tertile of baseline CSF CCL2 exhibited a shorter time period to conversion to dementia compared to those in the lowest tertile (p<0.003, Mann Whitney U test). The CCL2 tertiles were established in the whole MCI cohort (first tertile = 292–584 pg/ml; second terile = 585–756 pg/ml; third tertile = 757–1369 pg/ml). Error bars indicate the standard error of the mean.
Figure 2 The disease progression rate is increased in cases with prodromal AD who have higher levels of CCL2 in the cerebrospinal fluid at baseline. Panel A shows that prodromal AD cases in the highest tertile of CSF CCL2 at baseline exhibited a significantly higher annual decrease in MMSE score during the follow-up period compared to those in the lowest tertile (p<0.001, Mann Whitney U test). Panel B depicts that prodromal AD cases in the highest tertile of baseline CSF CCL2 exhibited a shorter time period to conversion to dementia compared to those in the lowest tertile (p<0.003, Mann Whitney U test). The CCL2 tertiles were established in the whole MCI cohort (first tertile = 292–584 pg/ml; second terile = 585–756 pg/ml; third tertile = 757–1369 pg/ml). Error bars indicate the standard error of the mean.CC BY · PubMed Central
Figure 3 The clinical value of combining baseline levels of CSF CCL2 with standards CSF biomarkers (i.e. Tau, P-tau and Aβ42) in the whole MCI cohort. MCI patients with an AD-indicative CSF biomarker pattern (Tau>350 pg/ml and Aβ42/P-tau ratio <6.5; red squares) declined cognitively during follow-up, because many of these patients developed AD dementia, which was not the case for those with a normal CSF biomarker pattern (green circles). Importantly, the disease progression rate was significantly higher in MCI patients with an AD-indicative CSF biomarker pattern, who also had high CCL2 levels (in the third tertile) when compared to those who exhibited lower levels (in the first tertile) (p<0.05).
Figure 3 The clinical value of combining baseline levels of CSF CCL2 with standards CSF biomarkers (i.e. Tau, P-tau and Aβ42) in the whole MCI cohort. MCI patients with an AD-indicative CSF biomarker pattern (Tau>350 pg/ml and Aβ42/P-tau ratio <6.5; red squares) declined cognitively during follow-up, because many of these patients developed AD dementia, which was not the case for those with a normal CSF biomarker pattern (green circles). Importantly, the disease progression rate was significantly higher in MCI patients with an AD-indicative CSF biomarker pattern, who also had high CCL2 levels (in the third tertile) when compared to those who exhibited lower levels (in the first tertile) (p<0.05).CC BY · PubMed Central

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Metadata

Authors
Westin, K., Buchhave, P., Nielsen, H., Minthon, L., Janciauskiene, S., & Hansson, O.
Affiliations
  • Lund University (SE)
  • Medizinische Hochschule Hannover (DE)
Corresponding author
Hansson, Oskar
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-01-30
Volume
7
Issue
1
Pages
e30525
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0030525
PMC
PMC3268759
OpenAlex
W2135955660
Cited by
277
References
28
Citations by year
2026: 15 · 2025: 15 · 2024: 30 · 2023: 11 · 2022: 29 · 2021: 27 · 2020: 21 · 2019: 20 · 2018: 11 · 2017: 23 · 2016: 10 · 2015: 18 · 2014: 21 · 2013: 21 · 2012: 5
FWCI
13.94
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Lund University Publications (Lund University) (submittedVersion, other-oa)
Funders
  • Skåne County Council's Research and Development Foundation
  • Vetenskapsrådet
  • Swedish Brain Power
  • Socialstyrelsen
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
MCP-1, CCR2, Alzheimer's disease, mild cognitive impairment, cognitive decline, cerebrospinal fluid biomarkers, CCL26, eotaxin, CCL13, conversion to Alzheimer's disease, tau protein, phosphorylated tau, amyloid-beta 42, disease progression prediction, chemokine signaling, neuroinflammation
MeSH terms
Aged, Alzheimer Disease, Cognition Disorders, Demography, Female, Follow-Up Studies, Humans, Male, Cohort Studies, Biomarkers, Linear Models, Disease Progression, Chemokine CCL2, Cognitive Dysfunction

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