CCL2 is associated with a faster rate of cognitive decline during early stages of Alzheimer's disease.
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.
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Karin
K
Westin
Peder
P
Buchhave
Henrietta
H
Nielsen
Lennart
L
Minthon
Sabina
S
Janciauskiene
Oskar
O
Hansson
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000150:complications; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D018932:Chemokine CCL2 / Q000097:blood* / Q000134:cerebrospinal fluid*; D003072:Cognition Disorders / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000150:complications; D060825:Cognitive Dysfunction / Q000097:blood / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D003710:Demography; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016014:Linear Models; D008297:Male
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2