ANALYSIS OF STRUCTURAL BRAIN CHANGES IN SUBJECTS FROM PRESYMPTOMATIC TO ADVANCED HUNTINGTON’S DISEASE

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by a CAG trinucleotide repeat expansion mutation. The number of CAG repeats is a major determinant of the age at onset of HD and other poly(CAG) diseases. For years before unequivocal disease manifestations of HD develop, many mutation carriers have “soft” motor signs associated with subtle behavioral and neuropsychological changes. Disease progression is weakly dependent on CAG length but is closely related to progressive neuronal loss in the striatum. Although the striatum has for long been considered the cerebral area most frequently involved in HD, more recent reports have highlighted widespread cortical and subcortical brain atrophy and functional cortical brain changes early in the disease course. Early research on HD focused on volumetric changes in brain grey matter, mostly involving the basal ganglia and cortex. More recent studies have reported cortical and striatal atrophy, and changes in brain white matter. The difficulties in ascertaining and studying subjects in the presymptomatic stages (HD mutation carriers) and in obtaining both structural and functional data from an identical cohort of patients have left open the key questions whether brain atrophy and hypometabolism start before the clinical symptoms and if so, by how long they precede the disease onset. The discovery of cerebral markers revealing presymptomatic neuropathological events possibly occurring before manifested symptoms of HD would be crucial for any attempt of therapeutic preventive treatment. At present in HD no biomarkers are available for monitoring preventive treatments.