title: Mutant huntingtin is present in neuronal grafts in Huntington disease patients.
abstract: OBJECTIVE
  Huntington disease (HD) is caused by a genetically encoded pathological protein (mutant huntingtin [mHtt]), which is thought to exert its effects in a cell-autonomous manner. Here, we tested the hypothesis that mHtt is capable of spreading within cerebral tissue by examining genetically unrelated fetal neural allografts within the brains of patients with advancing HD.
  
  
  METHODS
  The presence of mHtt aggregates within the grafted tissue was confirmed using 3 different types of microscopy (bright-field, fluorescence, and electron), 2 additional techniques consisting of Western immunoblotting and infrared spectroscopy, and 4 distinct antibodies targeting different epitopes of mHtt aggregates.
  
  
  RESULTS
  We describe the presence of mHtt aggregates within intracerebral allografts of striatal tissue in 3 HD patients who received their transplants approximately 1 decade earlier and then died secondary to the progression of their disease. The mHtt(+) aggregates were observed in the extracellular matrix of the transplanted tissue, whereas in the host brain they were seen in neurons, neuropil, extracellular matrix, and blood vessels.
  
  
  CONCLUSIONS
  This is the first demonstration of the presence of mHtt in genetically normal and unrelated allografted neural tissue transplanted into the brain of affected HD patients. These observations raise questions on protein spread in monogenic neurodegenerative disorders of the central nervous system characterized by the formation of mutant protein oligomers/aggregates.
authors.affiliation: Centre Hospitalier Universitaire de Québec Research Center; Departments of Psychiatry and Neurosciences.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cicchetti
authors.forename: Steve
authors.initials: S
authors.lastname: Lacroix
authors.forename: Giulia
authors.initials: G
authors.lastname: Cisbani
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vallières
authors.forename: Martine
authors.initials: M
authors.lastname: Saint-Pierre
authors.forename: Isabelle
authors.initials: I
authors.lastname: St-Amour
authors.forename: Ranna
authors.initials: R
authors.lastname: Tolouei
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Skepper
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.forename: Diego
authors.initials: D
authors.lastname: Mantovani
authors.forename: Roger A
authors.initials: RA
authors.lastname: Barker
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Freeman
mesh_terms: D000328:Adult; D064591:Allografts / Q000378:metabolism*; D016380:Brain Tissue Transplantation; D002986:Clinical Trials as Topic / Q000639:trends; D016332:Fetal Tissue Transplantation; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D017072:Neostriatum / Q000196:embryology / Q000637:transplantation; D009419:Nerve Tissue Proteins / Q000235:genetics*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins