Abstract
Biomarkers of Huntington’s disease (HD) in cerebrospinal fluid (CSF) could be of value in elucidating the biology of this genetic neurodegenerative disease, as well as in the development of novel therapeutics. Deranged synaptic and immune function have been reported in HD, and concentrations of the synaptic protein neurogranin and the microglial protein TREM2 are increased in other neurodegenerative diseases. We therefore used ELISAs to quantify neurogranin and TREM2 in CSF samples from HD mutation carriers and controls. CSF neurogranin concentration was not significantly altered in HD compared to controls, nor was it significantly associated with disease burden score, total functional capacity or motor score. An apparent increase in CSF TREM2 in manifest HD was determined to be due to increasing TREM2 with age. After age adjustment, there was no significant alteration of TREM2 in either HD group, nor any association with motor, functional or cognitive score, or brain volume quantified by MRI. Both analyses were well-powered, and sample size calculations indicated that several thousand samples per group would be needed to prove that disease-associated alterations do in fact exist. We conclude that neither neurogranin nor TREM2 is a useful biofluid biomarker for disease processes in Huntington’s disease.
Highlights
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansions in HTT encoding mutant huntingtin protein[1]
Triggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor expressed by myeloid cells including monocytes, macrophages and microglia whose activation is inhibitory to the immune response[19]
There was no significant correlation between cerebrospinal fluid (CSF) neurogranin levels and disease burden score, Unified Huntington’s Disease Rating Scale (UHDRS) total functional capacity score or UHDRS total motor score
Summary
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansions in HTT encoding mutant huntingtin protein[1]. Group (n) Age Sex F/M CAG Disease burden score Total functional capacity Total motor score CSF TREM2 concentration (√pg/mL) CSF neurogranin concentration was not significantly different between healthy controls and HD (Fig. 1; p = 1.000).
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