New insights into the pathoanatomy of spinocerebellar ataxia type 3 (Machado–Joseph disease)

PURPOSE OF REVIEW: This review summarizes recent neuropathological findings in spinocerebellar ataxia type 3 and discusses their relevance for clinical neurology. RECENT FINDINGS: The extent of the spinocerebellar ataxia type 3 related central nervous neurodegenerative changes has been recently systematically investigated in a series of pathoanatomical studies. These studies showed that the extent of the central nervous degenerative changes of spinocerebellar ataxia type 3 has been underestimated so far. The newly described pattern of central nervous neurodegeneration includes the visual, auditory, vestibular, somatosensory, ingestion-related, dopaminergic and cholinergic systems. These pathological findings were correlated with clinical findings and explain a variety of the spinocerebellar ataxia type 3 symptoms observed in clinical practice. SUMMARY: Systematic pathoanatomical analysis of spinocerebellar ataxia type 3 brains helps to understand the structural basis of this neurodegenerative disease and offers explanations for a variety of disease symptoms. This better understanding of the neuropathology of the condition has implications for the treatment of spinocerebellar ataxia type 3 patients and represents a basis for further biochemical and molecular biological studies aimed at deciphering the pathomechanisms of this progressive ataxic disorder.