-Cerebrospinal fluid (CSF) biomarkers: Analysis of CSF can reveal changes in levels of certain proteins associated with neurodegeneration, such as tau, neurofilament light chain (NfL), and specific fragments of huntingtin protein in Huntington's disease. In another example, cocaine-and amphetamine-regulated transcript (CART) is reported elevated in CSF of HD patients, possibly due to the pathogenic lesions in the hypothalamus. The oxidative stress marker F2-isoprostane is also increased in CSF from HD patients. 174 CSF levels of homovanillic acid are declined in CSF samples from HD, SCA1, and SCA3 patients, as a result of the altered dopamine metabolism. Lactate/pyruvate ratio is elevated in CSF of HD and SCA3 patients. -Peripheral biomarkers: Blood-based biomarkers are of particular interest due to their non-invasive nature. These may include levels of mutant protein fragments, microRNAs, or other molecular signatures indicative of disease status. Given the implication of mitochondrial damage in the pathogenesis of HD and other polyQ diseases, causes of oxidative stress are plausible markers to monitor disease progression. For example, the serum level of 8hydroxydeoxyguanosine (8-OHdG), an indicator of oxidative damage to DNA, has been found increased in HD patients. The amounts of mitochondrial DNA from leukocytes, which is another marker of oxidative stress, has declined in the blood from patients with polyglutamine diseases. -Neuroimaging markers: Techniques like MRI can detect structural changes in the brain associated with polyQ diseases, such as cortical atrophy, white matter abnormalities, or changes in specific brain regions affected by the disease.