Mutant huntingtin is present in neuronal grafts in Huntington disease patients

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Bibtex

@article{a2db8865c5f94617b1b0784739d540c8,
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.INTERPRETATION: 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.",
keywords = "Adult, Allografts, Brain Tissue Transplantation, Clinical Trials as Topic, Fetal Tissue Transplantation, Humans, Huntington Disease, Middle Aged, Mutation, Neostriatum, Nerve Tissue Proteins, Journal Article, Research Support, Non-U.S. Gov't",
author = "Francesca Cicchetti and Steve Lacroix and Giulia Cisbani and Nicolas Valli{\`e}res and Martine Saint-Pierre and Isabelle St-Amour and Ranna Tolouei and Skepper, {Jeremy N} and Hauser, {Robert A} and Diego Mantovani and Barker, {Roger A} and Freeman, {Thomas B}",
note = "{\circledC} 2014 American Neurological Association.",
year = "2014",
month = "7",
doi = "10.1002/ana.24174",
language = "English",
volume = "76",
pages = "31--42",
journal = "Annals of Neurology",
issn = "1531-8249",
publisher = "John Wiley and Sons Inc.",
number = "1",

}