CHI3L1 (YKL-40) and Chit-1 expressing glia in the white matter of ALS, FTLD and AD: correlations to pathology and disease duration.

BACKGROUND

Chitotriosidase (Chit-1) and chitinase-3-like protein 1 (CHI3L1) protein levels are increased in the cerebrospinal fluid (CSF) of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Alzheimer's disease (AD). Few studies have examined the spatial expression of chitinase-expressing cells with respect to neuropathologic hallmarks of disease.

METHODS

RNA sequencing was used to examine Chit-1 and CHI3L1 gene expression in the spinal cord and motor cortex. Immunohistochemistry was used to characterise the distribution of Chit-1 and CHI3L1 expressing cells in ALS, C9-ALS, FTLD, AD and non-neurologic disease controls. Immunofluorescence confocal microscopy was used to correlate distribution of Chit-1 and CHI3L1 expressing cells to TDP-43 pathology.

RESULTS

Chit-1 gene expression was increased in the spinal cord, and CHI3L1 expression was increased in both the spinal cord and motor cortex of patients with sALS and C9-ALS when compared with controls. Highest levels of Chit-1+ glia were in cortical regions that contain hallmark neuropathology for each neurodegenerative disease. CHI3L1+ glia were only significantly increased in sALS. Neither Chit-1+ nor CHI3L1+ glia was in close proximity to phosphorylated TDP-43 (pTDP) containing neurons in the motor cortex grey matter; however, there was a significant co-localisation of glial pTDP with Chit-1 and CHI3L1 in the motor cortex white matter.

CONCLUSIONS

Chit-1 and CHI3L1 expressing cells were most abundant in the white matter of cortical regions affected by each neurodegenerative disease and the spinal cord. Chit-1 or CHI3L1 expressing cells in the white matter often contained pTDP. We also observed correlations between levels of Chit-1 or CHI3L1 expressing cells in the white matter to disease duration.