In this study the investigators will link brain iron levels obtained from quantitative susceptibility maps of HD patients with specific and well-known clinical CSF markers for iron accumulation, neurodegeneration and neuroinflammation. The relationship between iron accumulation and neuroinflammation, and the clinical and genetic characteristics of HD will be investigated. This will provide an important basis for the evaluation of brain iron levels as an imaging biomarker for disease state in HD and their relationship with the salient pathomechanisms of the disease.

This investigator-initiated, single-site cross-sectional study looks at iron accumulation using 7T MR-imaging, CSF and blood. This will be achieved in a two-day visit involving clinical assessments, MRI-scanning of the brain, followed by a lumbar puncture the next day, after overnight fasting. Sixty-five volunteers with HD and 25 volunteers without HD will be included. Of these 65 volunteers with HD, 25 will be premanifest, 20 early manifest and 20 moderate manifest, in order to cover the wide-spectrum of Huntington's Disease.

Inclusion Criteria:

• Native Dutch/Flemish speaker
• Ability to undergo MRI scanning;
• Written informed consent must be obtained from the participant.

And in addition:

If the participant is a pre-manifest HD gene carrier:

• CAG expansion ≥ 40;
• UHDRS Total Motor Score (TMS) ≤ 5;
• Total Functional Capacity (TFC) = 13;
• Diagnostic Confidence Score < 4.

If the participant is an early-manifest HD gene carrier:

• CAG expansion ≥ 36;
• Diagnostic Confidence Score = 4;
• HD stage I: TFC scores between 11 and 13 inclusive.

If the participant is a moderate manifest HD gene carrier:

• CAG expansion ≥ 36;
• Diagnostic Confidence Score = 4;
• HD stage II: TFC scores between 7 and 11 inclusive.

If the participant is a control subject:

• Partner/spouse of a patient not at risk of HD OR sibling with genetic test results available that show a normal CAG repeat length for both HTT alleles (<36);
• No other known cognitive, neurological or psychiatric disorders.

Exclusion Criteria:

• Additional major comorbidities not related to HD (e.g. cardiovascular diseases, coagulopathy, hypertension, diabetes mellitus, and/or other neurological disorders);

• History of severe head injury;

• Status of the participant after brain surgery;

• Past erythrocyte transfusions;

• Use of investigational drugs or participation in a clinical drug trial within 30 days prior to study visit;

• Current intoxication, drug or alcohol abuse or dependence;

• Pregnancy;

• Inability to understand the information about the protocol;

• Severe physical restrictions (completely wheelchair dependent);

• Severe chorea that, in the investigator's judgment, precludes the patient's participation in and completion of the MRI and/or lumbar puncture.

• Contra-indication to MRI scanning, such as:

  • Claustrophobia;
  • Pacemakers and defibrillators;
  • Nerve stimulators;
  • Intracranial clips;
  • Intraorbital or intraocular metallic fragments;
  • Cochlear implants;
  • Ferromagnetic implants;
  • Hydrocephalus pump;
  • Intra-utrine device (not all types);
  • Permanent make-up;
  • Tattoos above the shoulders (not all).

• Contraindications for a lumbar puncture, including:

  • Screening blood test results outside normal ranges(white cell count, neutrophil count, lymphocyte count, hemoglobin, platelets, Prothrombin time (PT), activated partial thromboplastin time (APTT), C-reactive protein (CRP) and serum ferritin) if only marginally decreased or increased this will be decided by the clinical PI;
  • Signs and symptoms of increased intracranial pressure which will be confirmed on the 7T MRI (T1 and FLAIR scan) or by a fundoscopy;
  • Local infections of the skin;
  • Use of anti-coagulant drugs within the last 14 days prior lumbar puncture.

Pre-manifest HD gene carrier:

• CAG expansion ≥ 40;
• UHDRS Total Motor Score (TMS) ≤ 5;
• Total Functional Capacity (TFC) = 13;
• Diagnostic Confidence Score < 4.

Early-manifest HD gene carrier:

• CAG expansion ≥ 36;
• Diagnostic Confidence Score = 4;
• HD stage I: TFC scores between 11 and 13 inclusive.

Moderate manifest HD gene carrier:

• CAG expansion ≥ 36;
• Diagnostic Confidence Score = 4;
• HD stage II: TFC scores between 7 and 10

Control subject:

• Partner/spouse of a patient not at risk of HD OR sibling with genetic test results available that show a normal CAG repeat length for both HTT alleles (<36);
• No other known cognitive, neurological or psychiatric disorders.