Untangling the Role of Tau in Huntington’s Disease Pathology

There is increasing evidence for the presence of pathological forms of tau in tissues of both Huntington’s disease (HD) patients and animal models of this condition. While cumulative studies of the past decade have led to the proposition that this disorder could also be considered a tauopathy, the implications of tau in cellular toxicity and consequent behavioral impairments are largely unknown. In fact, recent animal work has challenged the contributory role of tau in HD pathogenesis/pathophysiology. This review presents the supporting and opposing arguments for the involvement of tau in HD, highlighting the discrepancies that have emerged. Reflecting on what is known in other tauopathies, the putative mechanisms through which tau could initiate and/or contribute to pathology are discussed, shedding light on the future research directions that could be considered to confirm, or rule out, the clinical relevance of tau in HD.