Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder of 
the central nervous system (CNS) that is defined by a CAG expansion in exon 1 of 
the huntingtin gene leading to the production of mutant huntingtin (mHtt). To 
date, the disease pathophysiology has been thought to be primarily driven by 
cell-autonomous mechanisms, but, here, we demonstrate that fibroblasts derived 
from HD patients carrying either 72, 143 and 180 CAG repeats as well as induced 
pluripotent stem cells (iPSCs) also characterized by 143 CAG repeats can 
transmit protein aggregates to genetically unrelated and healthy host tissue 
following implantation into the cerebral ventricles of neonatal mice in a 
non-cell-autonomous fashion. Transmitted mHtt aggregates gave rise to both motor 
and cognitive impairments, loss of striatal medium spiny neurons, increased 
inflammation and gliosis in associated brain regions, thereby recapitulating the 
behavioural and pathological phenotypes which characterizes HD. In addition, 
both in vitro work using co-cultures of mouse neural stem cells with 143 CAG 
fibroblasts and the SH-SY5Y human neuroblastoma cell line as well as in vivo 
experiments conducted in newborn wild-type mice suggest that exosomes can cargo 
mHtt between cells triggering the manifestation of HD-related behaviour and 
pathology. This is the first evidence of human-to-mouse prion-like propagation 
of mHtt in the mammalian brain; a finding which will help unravel the molecular 
bases of HD pathology as well as to lead to the development of a whole new range 
of therapies for neurodegenerative diseases of the CNS.