title: Huntington's disease (HD): the neuropathology of a multisystem neurodegenerative disorder of the human brain.
abstract: Huntington's disease (HD) is an autosomal dominantly inherited, and currently untreatable, neuropsychiatric disorder. This progressive and ultimately fatal disease is named after the American physician George Huntington and according to the underlying molecular biological mechanisms is assigned to the human polyglutamine or CAG-repeat diseases. In the present article we give an overview of the currently known neurodegenerative hallmarks of the brains of HD patients. Subsequent to recent pathoanatomical studies the prevailing reductionistic concept of HD as a human neurodegenerative disease, which is primarily and more or less exclusively confined to the striatum (ie, caudate nucleus and putamen) has been abandoned. Many recent studies have improved our neuropathological knowledge of HD; many of the early groundbreaking findings of neuropathological HD research have been rediscovered and confirmed. The results of this investigation have led to the stepwise revision of the simplified pathoanatomical and pathophysiological HD concept and culminated in the implementation of the current concept of HD as a multisystem degenerative disease of the human brain. The multisystem character of the neuropathology of HD is emphasized by a brain distribution pattern of neurodegeneration (i) which apart from the striatum includes the cerebral neo-and allocortex, thalamus, pallidum, brainstem and cerebellum, and which (ii) therefore, shares more similarities with polyglutamine spinocerebellar ataxias than previously thought.
authors.affiliation: Dr. Senckenbergisches Chronomedizinisches Institut, Goethe-University, Frankfurt/Main, D-60590, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Rüb
authors.affiliation: Dr. Senckenbergisches Chronomedizinisches Institut, Goethe-University, Frankfurt/Main, D-60590, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Seidel
authors.affiliation: Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil.|Morphological Brain Research Unit, Psychiatric Clinic, Julius Maximilians University Würzburg, Würzburg, D-97080, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Heinsen
authors.affiliation: The New York Brain Bank/Taub Institute, The Presbyterian Hospital and Columbia University, New York, NY.
authors.forename: J P
authors.initials: JP
authors.lastname: Vonsattel
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen University of Groningen, RB Groningen, NL-5970, The Netherlands.
authors.forename: W F
authors.initials: WF
authors.lastname: den Dunnen
authors.affiliation: Dr. Senckenbergisches Chronomedizinisches Institut, Goethe-University, Frankfurt/Main, D-60590, Germany.
authors.forename: H W
authors.initials: HW
authors.lastname: Korf
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics / Q000378:metabolism; D006816:Huntington Disease / Q000150:complications / Q000235:genetics / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000150:complications / Q000473:pathology*; D010455:Peptides / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; C118585:P62 protein, human; D010455:Peptides; D016601:RNA-Binding Proteins; C097188:polyglutamine
keywords: brainstem; cerebellum; cerebral cortex; pathoanatomy; polyglutamine diseases; thalamus