Decreased cerebral ATP in pre-motor manifest Huntington's disease: A pilot study

Lindsay E Golden; Jia Xu; Vincent A Magnotta; Peg C Nopoulos; Jordan L Schultz

doi:10.1016/j.parkreldis.2025.108040

Decreased cerebral ATP in pre-motor manifest Huntington's disease: A pilot study

Parkinsonism Relat Disord. 2025 Nov:140:108040. doi: 10.1016/j.parkreldis.2025.108040. Epub 2025 Sep 15.

Authors

Lindsay E Golden¹, Jia Xu², Vincent A Magnotta³, Peg C Nopoulos⁴, Jordan L Schultz⁵

Affiliations

¹ Carver College of Medicine at the University of Iowa, Department of Psychiatry, 200 Hawkins Drive, Iowa City, IA, 52242, USA. Electronic address: Lindsay-golden@uiowa.edu.
² Carver College of Medicine at the University of Iowa, Department of Radiology, 200 Hawkins Drive, Iowa City, IA, 52242, USA.
³ Carver College of Medicine at the University of Iowa, Department of Psychiatry, 200 Hawkins Drive, Iowa City, IA, 52242, USA; Carver College of Medicine at the University of Iowa, Department of Radiology, 200 Hawkins Drive, Iowa City, IA, 52242, USA.
⁴ Carver College of Medicine at the University of Iowa, Department of Psychiatry, 200 Hawkins Drive, Iowa City, IA, 52242, USA; Carver College of Medicine at the University of Iowa, Department of Neurology, 200 Hawkins Drive, Iowa City, IA, 52242, USA; Stead Family Department of Pediatrics at the University of Iowa, 200 Hawkins Drive, Iowa City, IA, 52242, USA.
⁵ Carver College of Medicine at the University of Iowa, Department of Psychiatry, 200 Hawkins Drive, Iowa City, IA, 52242, USA; Carver College of Medicine at the University of Iowa, Department of Neurology, 200 Hawkins Drive, Iowa City, IA, 52242, USA; The University of Iowa College of Pharmacy, Department of Pharmacy Practice and Science, 115 S. Grand Ave, Iowa City, IA, 52242, USA.

PMID: 40974859
DOI: 10.1016/j.parkreldis.2025.108040

Abstract

Background: Huntington's Disease (HD) is characterized by brain metabolic dysfunction, but no studies to date have directly measured cerebral ATP levels in patients with HD.

Objective: To compare cerebral ATP between individuals with pre-motor-manifest HD (preHD) and healthy controls (HC).

Methods: Cerebral ATP was quantified using ³¹Phosphorous Magnetic Resonance Spectroscopy (³¹P-MRS) at 7T in nine preHD subjects and nine HC subjects. Analysis of Covariance models were constructed to compare mean ATP signal (corrected by whole brain volume) between groups after adjusting for age and BMI.

Results: PreHD participants exhibited significantly lower total ATP compared to HCs; furthermore, preHD subjects with higher clinical burden of disease had lower ATP levels. Amongst the preHD subjects, lower ATP levels were associated with worsening composite Unified Huntington's Disease Rating Scale scores.

Conclusions: Our findings highlight the potential of ³¹P-MRS to serve as a direct assay for metabolic dysfunction in HD.

MeSH terms

Adenosine Triphosphate* / metabolism
Adult
Cerebral Cortex* / diagnostic imaging
Cerebral Cortex* / metabolism
Female
Humans
Huntington Disease* / diagnostic imaging
Huntington Disease* / metabolism
Magnetic Resonance Spectroscopy
Male
Middle Aged
Pilot Projects

Substances

Adenosine Triphosphate