Abstract:
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.
journal_name
Ann Clin Transl Neuroljournal_title
Annals of clinical and translational neurologyauthors
Gray E,Thompson AG,Wuu J,Pelt J,Talbot K,Benatar M,Turner MRdoi
10.1002/acn3.51114subject
Has Abstractpub_date
2020-08-01 00:00:00pages
1296-1306issue
8issn
2328-9503journal_volume
7pub_type
杂志文章abstract:OBJECTIVE:To evaluate whether structural and microstructural brain abnormalities in neonates with congenital heart disease (CHD) correlate with neuronal network dysfunction measured by analysis of EEG connectivity. METHODS:We studied a prospective cohort of 20 neonates with CHD who underwent continuous EEG monitoring ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.336
更新日期:2016-08-14 00:00:00
abstract:OBJECTIVES:The distribution of pathology in neurodegenerative disease can be predicted by the organizational characteristics of white matter in healthy brains. However, we have very little evidence for the impact these pathological changes have on brain function. Understanding any such link between structure and functi...
journal_title:Annals of clinical and translational neurology
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abstract::Aicardi-Goutières syndrome is a leukoencephalopathy with calcifications and increased cerebrospinal fluid interferon-α. The relation between interferon-α and brain pathology is poorly understood. We report a patient with mutations in the disease-associated gene SAMHD1. Neuropathology showed an extensive microangiopath...
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更新日期:2015-07-01 00:00:00
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journal_title:Annals of clinical and translational neurology
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更新日期:2016-06-02 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
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更新日期:2014-05-01 00:00:00
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更新日期:2017-04-26 00:00:00
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journal_title:Annals of clinical and translational neurology
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更新日期:2014-09-01 00:00:00
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doi:10.1002/acn3.503
更新日期:2017-11-24 00:00:00
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pub_type: 杂志文章
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更新日期:2019-03-07 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.447
更新日期:2017-09-08 00:00:00
abstract::Prenatal exposure to sodium valproate (VPA) is associated with neurodevelopmental impairments. Cortical thickness was measured in 16 children exposed prenatally to VPA and 16 controls. We found increased left inferior frontal gyrus (IFG; BA45) and left pericalcarine sulcus (BA18) thickness, an association between VPA ...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.74
更新日期:2014-07-01 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.47
更新日期:2014-05-01 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.540
更新日期:2018-03-01 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type:
doi:10.1002/acn3.50995
更新日期:2020-03-01 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50889
更新日期:2019-10-01 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50833
更新日期:2019-09-01 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50888
更新日期:2019-09-01 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.776
更新日期:2019-04-08 00:00:00
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pub_type: 杂志文章
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51179
更新日期:2020-12-18 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.595
更新日期:2018-07-03 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.86
更新日期:2014-08-01 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51153
更新日期:2020-10-01 00:00:00
abstract:Objective:Limited attention has been given to ocular injuries associated with traumatic brain injury (TBI). The retina is an extension of the central nervous system and evaluation of ocular damage may offer a less-invasive approach to gauge TBI severity and response to treatment. We aim to characterize acute changes in...
journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.523
更新日期:2018-02-26 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50837
更新日期:2019-08-01 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.50912
更新日期:2019-11-01 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
doi:10.1002/acn3.51073
更新日期:2020-06-01 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type: 杂志文章
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更新日期:2016-02-02 00:00:00
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journal_title:Annals of clinical and translational neurology
pub_type:
doi:10.1002/acn3.51160
更新日期:2020-09-01 00:00:00