The primary objective of this study is to discover blood-based biomarker of brain Huntingtin (HTT) protein using extracellular vesicles to be used in evaluating target engagement in HTT lowering clinical trials.

Secondary objectives of this study include developing more accurate biomarkers of Huntington disease (HD) progression or conversion and to develop standard practices for extracellular vesicle biomarker discovery research.

The investigators hypothesize that brain-derived extracellular vesicles (EVs) isolated from human biofluids contain biological cargo specific to their tissue of origin that could allow their use as brain biomarkers for HD. EVs are lipid bilayer-delimited particles that are naturally released from cells in the brain.

The investigators will investigate if EVs contents reflect the pathological alterations occurring with disease progression when compared with EVs isolated from biofluids of healthy non-HD persons.

Inclusion Criteria:

1. 18 - 75 years of age
2. can provide informed consent
3. able to read and speak English
4. agree to comply with study procedures (including overnight fasting, blood collection and lumbar puncture); and
5. has been diagnosed with HD (HD Carriers) or not been diagnosed with HD (Non-HD Carriers).

Exclusion Criteria:

1. younger than 18 or older than 75 years old
2. known to carry an intermediate CAG repeat between 27 and 39 or a larger expansion of 60 or more CAG repeats
3. receiving nutrition through a tube
4. pregnant
5. participated in a clinical drug trial within 30 days
6. use prescribed or non-prescribed medications that are not compatible with collection of the study samples (those that may cause excessive bleeding or prevent clotting)
7. positive for HIV, hepatitis B or C
8. have a confirmed or suspected immunodeficient condition/state
9. significant medical, psychiatric, or neurological morbidity is observed by the clinic physician on the day of sample collection that might impair completion of the study procedures
10. have needle phobia, frequent headache, significant lower spinal deformity or major surgery
11. received antiplatelet or anticoagulant therapy within 14 days prior to sample collection (including but not limited to: aspirin, clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban and apixaban)
12. have a blood clotting or bruising disorder
13. do not comply with or are unwilling to undertake any of the study procedures

The study will enroll HD carriers (HD Carriers) and non-carriers (Non-HD Carriers).

100 participants will be enrolled. 25 from Central Florida Center for Huntington Disease at the University of Central Florida (Orlando) and 75 from Huntington's Disease Center of Excellence at the University of South Florida (Tampa).