The Neuropathology of Huntington’s Disease: Classical Findings, Recent Developments and Correlation to Functional Neuroanatomy

Abstract

Advances in Anatomy, Embryology and Cell Biology publishes critical reviews and state-ofthe-art surveys on all aspects of anatomy and of developmental, cellular and molecular biology, with a special emphasis on biomedical and translational topics.The series publishes volumes in two different formats:• Contributed volumes, each collecting 5 to 15 focused reviews written by leading experts • Single-authored or multi-authored monographs, providing a comprehensive overview of their topic of research Manuscripts should be addressed to

Huntington's disease (HD): the neuropathology of a multisystem neurodegenerative disorder of the human brain

“…These pathologically elongated CAG‐repeat sequences are translated into abnormally long polyglutamine stretches in the mutated huntingtin protein. The pathological elongation of polyglutamine stretches in mutant huntingtin, in turn, are currently held to be responsible for the tendency of this multifunctional protein to lose its normal solubility in nerve cells and to aggregate into intra‐neuronal inclusions in different compartments of vulnerable brain regions (Figures and ) .…”

Deficits in temporal processing correlate with clinical progression in Huntington's disease

“…In the striatum, MSNs are most affected and degeneration of these neurons occurs progressively . Clinically, patients with HD present progressive motor dysfunction, cognitive decline and psychiatric disturbance with the age of onset inversely related to the repeat length . Cognitive impairment may develop years earlier than motor dysfunction, deteriorates over time and accounts for a significant portion of reduced functional capacity in patients with HD .…”

Pathoarchitectonics of the cerebral cortex in chorea‐acanthocytosis and Huntington's disease

“…Indeed, besides the neuronal loss in layers III, Vb and VI, our ChAc cases were characterized by striatal neurone loss, which exceeded that of our HD cases . Furthermore, there is evidence for an early cortical involvement in HD and it is still a matter of debate whether neurodegeneration of cortico‐striatal axons is causing dysfunction and degeneration of striatal neurones in an anterograde manner or retrograde and transneuronal pathways from the striatum and thalamus can induce cortical neurodegeneration. Shepherd discusses the yet unresolved role of intratelencephalic and pyramidal tract neurones and their disconnection in the pathophysiology of HD.…”

“…A reverse condition could be observed in terminal stages of HD, which were characterized by a high cell density and low cortical volume (Figure b , c and figure 3.2 in Rüb et al . ).…”

“…This contrasts with our late‐stage HD cases. In this stage, layer‐specific neurone loss resulted in pallor of gallocyanin‐stained sections, a pathognomonic horizontal striation and a characteristic neurone loss in allorcortical regions .…”