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. 2017 Sep 26;12(9):e0185541.
doi: 10.1371/journal.pone.0185541. eCollection 2017.

CCL11 is increased in the CNS in chronic traumatic encephalopathy but not in Alzheimer's disease

Jonathan D Cherry  1   2   3 , Thor D Stein  1   2   4 , Yorghos Tripodis  5 , Victor E Alvarez  1   2   3   4 , Bertrand R Huber  1   2   3 , Rhoda Au  2   6 , Patrick T Kiernan  1 , Daniel H Daneshvar  1 , Jesse Mez  1   2 , Todd M Solomon  1 , Michael L Alosco  1   2 , Ann C McKee  1   2   3   4   7
Affiliations

CCL11 is increased in the CNS in chronic traumatic encephalopathy but not in Alzheimer's disease

Jonathan D Cherry et al. PLoS One. .

Abstract

CCL11, a protein previously associated with age-associated cognitive decline, is observed to be increased in the brain and cerebrospinal fluid (CSF) in chronic traumatic encephalopathy (CTE) compared to Alzheimer's disease (AD). Using a cohort of 23 deceased American football players with neuropathologically verified CTE, 50 subjects with neuropathologically diagnosed AD, and 18 non-athlete controls, CCL11 was measured with ELISA in the dorsolateral frontal cortex (DLFC) and CSF. CCL11 levels were significantly increased in the DLFC in subjects with CTE (fold change = 1.234, p < 0.050) compared to non-athlete controls and AD subjects with out a history of head trauma. This increase was also seen to correlate with years of exposure to American football (β = 0.426, p = 0.048) independent of age (β = -0.046, p = 0.824). Preliminary analyses of a subset of subjects with available post-mortem CSF showed a trend for increased CCL11 among individuals with CTE (p = 0.069) mirroring the increase in the DLFC. Furthermore, an association between CSF CCL11 levels and the number of years exposed to football (β = 0.685, p = 0.040) was observed independent of age (β = -0.103, p = 0.716). Finally, a receiver operating characteristic (ROC) curve analysis demonstrated CSF CCL11 accurately distinguished CTE subjects from non-athlete controls and AD subjects (AUC = 0.839, 95% CI 0.62-1.058, p = 0.028). Overall, the current findings provide preliminary evidence that CCL11 may be a novel target for future CTE biomarker studies.

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Conflict of interest statement

Competing Interests: Dr. McKee reported that she has received funding from the NFL and WWE and is a member of the Mackey-White Committee of the NFL Players’ Association. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. All other authors report no conflicts of interest. This does not alter our adherence to the PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Protein levels of CCL11 are elevated in the DLFC in CTE but not AD.
CCL11 protein levels were measured using ELISA. CCL11 fold change is shown for non-exposed control, CTE, and AD subjects. Bar graphs shows mean ± SEM, *p < 0.05; One-way ANOVA.
Fig 2
Fig 2. CCL11 is elevated in cases with more than 16 years of exposure to American football.
CCL11 protein fold changes are shown for non-exposed controls (n = 18), cases with less than 16 years of exposure (n = 10), and cases with more than or equal to 16 years of exposure (n = 13). Bar graphs shows mean ± SEM, *p < 0.05, ***p < 0.001; One-way ANOVA.
Fig 3
Fig 3. CCL11 is elevated in the CSF during CTE.
(A) Quantitation of CCL11 fold change in the CSF is shown for control (n = 4), CTE (n = 7), and AD (n = 4) subjects. (B) Receiver operatic characteristic (ROC) curve for CSF CCL11 predicting CTE. Red line denotes CCL11 while the black line is the reference, AUC = 0.839, 95% CI 0.62–1.058, p = 0.028. Bar graphs shows mean ± SEM, One-way ANOVA.
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