Magnetic resonance spectroscopy biomarkers in premanifest and early Huntington disease.
OBJECTIVE
To evaluate in vivo brain metabolite differences in control subjects, individuals with premanifest Huntington disease (pre-HD), and individuals with early HD using ¹H magnetic resonance spectroscopy (MRS) and to assess their relationship with motor performance.


METHODS
Eighty-five participants (30 controls, 25 pre-HD, and 30 early HD) were recruited as part of the TRACK-HD study. Eighty-four were scanned at 3 T with single-voxel spectroscopy in the left putamen. Disease burden score was >220 among pre-HD individuals. Subjects underwent TRACK-HD motor assessment including Unified Huntington's Disease Rating Scale (UHDRS) motor scoring and a novel quantitative motor battery. Statistical analyses included linear regression and one-way analysis of variance.


RESULTS
Total N-acetylaspartate (tNAA), a neuronal integrity marker, was lower in early HD (∼15%) vs controls (p < 0.001). N-acetylaspartate (NAA), a constituent of tNAA, was lower in pre-HD (∼8%) and early HD (∼17%) vs controls (p < 0.05). The glial cell marker, myo-inositol (mI), was 50% higher in early HD vs pre-HD (p < 0.01). In early HD, mI correlated with UHDRS motor score (R² = 0.23, p < 0.05). Across pre-HD and early HD, tNAA correlated with performance on a tongue pressure task (R² = 0.30, p < 0.0001) and with disease burden score (R² = 0.17, p < 0.005).


CONCLUSIONS
We demonstrate lower putaminal tNAA in early HD compared to controls in a cross-section of subjects. A novel biomarker role for mI in early HD was also identified. These findings resolve disagreement in the literature about the role of MRS as an HD biomarker. We conclude that putaminal MRS measurements of NAA and mI are promising potential biomarkers of HD onset and progression.
Centre for Molecular Medicine & Therapeutics, Vancouver, BC, Canada.
A
A
Sturrock
C
C
Laule
J
J
Decolongon
R
R
Dar Santos
A J
AJ
Coleman
S
S
Creighton
N
N
Bechtel
R
R
Reilmann
M R
MR
Hayden
S J
SJ
Tabrizi
A L
AL
Mackay
B R
BR
Leavitt
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011699:Putamen / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D001224:Aspartic Acid; C000179:N-acetylaspartate