title: Seeking brain biomarkers for preventive therapy in Huntington disease.
abstract: Huntington disease (HD) is a severe incurable nervous system disease that generally has an onset age of around 35-50, and is caused by a dominantly transmitted expansion mutation. A genetic test allows persons at risk, i.e., offspring or siblings of affected individuals, to discover their genetic status. Unaffected mutation-positive subjects will manifest HD sometime during life. Despite major advances in research on pathogenic mechanisms, no studies have yet fully validated preventive therapy or biomarkers for use before the symptoms become clinically manifest. Seeking brain and peripheral biomarkers is a requisite to develop a cure for HD. Changes in the brain can be observed in vivo using methods such as structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), functional MRI (fMRI), and positron emission tomography (PET), detecting volumetric changes, microstructural and connectivity alterations, abnormalities in brain activity in response to specific tasks, and abnormalities in metabolism and receptor distribution. Although all these imaging techniques can detect early markers in asymptomatic HD gene carriers for premanifest screening and pharmacological responses to therapeutic interventions no single modality has yet provided and validated an optimal marker probably because this task requires an integrative multimodal imaging approach. In this article, we review the findings from imaging procedures in the attempt to identify potential brain markers, so-called dry biomarkers, for possible application to further, yet unavailable, neuroprotective preventive therapies for HD manifestations.
authors.affiliation: Department of Clinical Neuroscience, Stockholm Brain Institute, Karolinska Institutet, PET Centre, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Mouna
authors.initials: M
authors.lastname: Esmaeilzadeh
authors.forename: Andrea
authors.initials: A
authors.lastname: Ciarmiello
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Squitieri
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003952:Diagnostic Imaging / Q000379:methods / Q000639:trends; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis / Q000378:metabolism* / Q000517:prevention & control*; D011314:Preventive Health Services / Q000379:methods / Q000639:trends*; D017448:Receptors, Dopamine D2 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017448:Receptors, Dopamine D2; D005947:Glucose