UC San Diego

Huntington’s disease (HD), is an autosomal dominant disorder caused by an expansion of the CAG sequence in the huntingtin gene, which encodes the ubiquitously expressed Huntingtin (Htt) protein. Diminished motor function, cognition, and functional capacity are common symptoms. HD affects 10 in every 100,000 individuals in the US, with symptoms showing substantial variability in age at onset, severity and course of illness; thus warranting the need for reliable biomarkers to anticipate the onset of the disease and track its progression. The protein associated with the disease, huntingtin (Htt), is released into the extracellular fluid as neurodegeneration occurs in HD, and is thus a potentially useful

biomarker. It has been previously measured in CSF and blood plasma in HD; however, these are invasive techniques with varying yields. We therefore wondered if Htt protein could be reliably measured in saliva.

We assayed 98 saliva samples from manifest(HD), premanifest(PM), and age-matched normal control(NC) participants and found that salivary total Htt (tHtt) was significantly increased in HD saliva compared to NC. Salivary tHtt showed no gender effects and was significantly positively correlated with age in HD. As expected, tHtt levels had a positive correlation with motor symptoms and a negative correlation with cognitive ability and functional capacity in HD. Thus, tHtt protein can be reliably measured in human saliva and shows promise as a non-invasive clinically meaningful biomarker of disease progression in HD.