التفاصيل البيبلوغرافية
| العنوان: |
CSF chitinases before and after symptom onset in amyotrophic lateral sclerosis. |
| المؤلفون: |
Gray, Elizabeth, Thompson, Alexander G., Wuu, Joanne, Pelt, Joe, Talbot, Kevin, Benatar, Michael, Turner, Martin R. |
| المصدر: |
Annals of Clinical & Translational Neurology; Aug2020, Vol. 7 Issue 8, p1296-1306, 11p |
| مصطلحات موضوعية: |
AMYOTROPHIC lateral sclerosis, SYMPTOMS, GENETIC mutation, PATHOLOGY |
| مستخلص: |
Objective: To evaluate the CSF levels of chitinase proteins during the presymptomatic and early symptomatic phases of amyotrophic lateral sclerosis (ALS). Methods: CSF samples were obtained from 16 controls, 55 individuals at‐risk for ALS (including 18 carrying a mutation in C9ORF72, 33 in SOD1), 12 ALS patients, and 7 phenoconverters (individuals diagnosed with ALS during follow‐up). At‐risk individuals and phenoconverters were enrolled through the Pre‐fALS study, which includes individuals carrying an ALS‐associated gene mutation without disease manifestations at initial assessment. Longitudinal CSF collections, where possible, took place every 3‐12 months for ALS patients and every 1‐2 years for others. CSF levels of chitotriosidase 1 (CHIT1), chitinase‐3‐like protein 1 (CHI3L1, YKL‐40) and chitinase‐3‐like protein 2 (CHI3L2, YKL‐39) were measured by ELISA, along with CHIT1 activity. Longitudinal changes in at‐risk individuals and phenoconverters were fitted to linear mixed effects models. Results: Slowly rising levels of CHIT1 were observed over time in the at‐risk individuals (slope 0.059 log10[CHIT1] per year, P < 0.001). Among phenoconverters, CHIT1 levels and activity rose more sharply (0.403 log10[CHIT1] per year, P = 0.005; 0.260 log10[CHIT1 activity] per year, P = 0.007). Individual levels of both CHI3L1 and CHI3L2 remained relatively stable over time in all participant groups. Interpretation: The CHIT1 neuroinflammatory response is a feature of the late presymptomatic to early symptomatic phases of ALS. This study does not suggest a long prodrome of upregulated glial activity in ALS pathogenesis, but strengthens the place of CHIT1 as part of a panel of biomarkers to objectively assess the impact of immune‐modulatory therapeutic interventions in ALS. [ABSTRACT FROM AUTHOR] |
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