A Glimpse of Molecular Biomarkers in Huntington’s Disease

Abstract

Huntington’s disease (HD) is a devastating neurodegenerative disorder that is caused by an abnormal expansion of CAG repeats in the Huntingtin (HTT) gene. Although the main symptomatology is explained by alterations at the level of the central nervous system, predominantly affecting the basal ganglia, a peripheral component of the disease is being increasingly acknowledged. Therefore, the manifestation of the disease is complex and variable among CAG expansion carriers, introducing uncertainty in the appearance of specific signs, age of onset and severity of disease. The monogenic nature of the disorder allows a precise diagnosis, but the use of biomarkers with prognostic value is still needed to achieve clinical management of the patients in an individual manner. In addition, we need tools to evaluate the patient’s response to potential therapeutic approaches. In this review, we provide a succinct summary of the most interesting molecular biomarkers that have been assessed in patients, mostly obtained from body fluids such as cerebrospinal fluid, peripheral blood and saliva.

The updated development of blood-based biomarkers for Huntington’s disease

“…The application of single-molecule assay made the quantification of Nfl possible and reliable in blood samples first in 2015 [ 71 ]. And after that, the role of peripheral Nfl level as a potential robust biomarker for HD has been investigated extensively and profoundly [ 72 , 73 ]. As plasma Nfl is widely supposed to be originated from CNS neuronal injuries and associated with CSF Nfl level [ 71 , 74 – 76 ], it is quite valuable and encouraging for a peripheral biofluid biomarker to reflect central pathogenesis, paving the way for its future presumable application in stratifying HD mutation carriers through identification of particular disease stage, especially for premanifest patients, reflecting or even predicting the neuropathological and clinical progression and indicating the therapeutic effect as an outcome measure of clinical trials.…”

Salivary analysis: An emerging paradigm for non‐invasive healthcare diagnosis and monitoring

“…Genetic analysis of saliva involves the identification and quantification of specific genetic markers or variations in saliva samples. These genetic biomarkers or variations are typically identified and quantified using techniques such as polymerase chain reaction (PCR) or next‐generation sequencing. Inherited disease biomarkers : Inherited genetic mutations can lead to the development of diseases such as cystic fibrosis, sickle cell anemia, and Huntington's disease 89 . Salivary genetic biomarkers have been investigated as a potential tool for diagnosing and monitoring these inherited diseases. Cancer biomarkers : Salivary genetic biomarkers have been investigated as a potential tool for diagnosing and monitoring cancers.…”

“…Inherited disease biomarkers : Inherited genetic mutations can lead to the development of diseases such as cystic fibrosis, sickle cell anemia, and Huntington's disease 89 . Salivary genetic biomarkers have been investigated as a potential tool for diagnosing and monitoring these inherited diseases.…”

Use of 3D Printing Techniques to Fabricate Implantable Microelectrodes for Electrochemical Detection of Biomarkers in the Early Diagnosis of Cardiovascular and Neurodegenerative Diseases

“…Recent studies have also identified potential biomarkers for other neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Huntington’s disease, and multiple sclerosis − These biomarkers include glial fibrillary acidic protein and myelin essential protein, which are indicative of neuronal damage, inflammation, and demyelination, respectively , …”