Amyloid-like inclusions in Huntington's disease

Huntington's disease is a progressive, autosomal dominantly inherited, neur odegenerative disease that is characterized by involuntary movements (chore a), cognitive decline and psychiatric manifestations.(7) This is one of a n umber of late-onset neurodegenerative disorders caused by expanded glutamin e repeats, with a likely similar biochemical basis.(9) Immunohistochemical studies on Huntington's disease tissue, using antibodies raised to the N-te rminal region of huntingtin (adjacent to the repeat) and ubiquitin, have re cently identified neuronal inclusions within densely stained neuronal nucle i, peri-nuclear and within dystrophic neuritic processes.' (1,3,6) However, the functional significance of inclusions is unknown. It has been suggeste d that the disease-causing mechanism in Huntington's disease (and the other polyglutamine disorders) is the ability of polyglutamine to undergo a conf ormational change that can lead to the formation of very stable anti-parall el beta -sheets; more specifically, amyloid structures.(13) We examined, us ing Congo Red staining and both polarizing and confocal microscopy, post mo rtem human brain tissue from five Huntington's disease cases, two Alzheimer 's disease cases and two normal controls. Brains from five transgenic mice (R6/2)(12) expressing exon 1 of the human huntingtin gene with expanded pol yglutamine, and five littermate controls, were also examined by the same te chniques. We have shown that some inclusions in Huntington's disease brain tissue possess an amyloid-like structure, suggesting parallels with other a myloid-associated diseases such as Alzheimer's and prion diseases. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.