. Author manuscript; available in PMC: 2015 Feb 1.

Published in final edited form as: Nat Rev Neurosci. 2015 Jan 15;16(2):109–120. doi: 10.1038/nrn3887

Table 1.

Summary of evidence supporting the propagation and transmission of non-prion neurodegenerative disease proteins

Pathogenic protein	Associated diseases in humans	Main localization of protein		Studies in human tissue supporting sequential spread	References supporting neuron-neuron transmission
Pathogenic protein	Associated diseases in humans	Wild-type	Pathological	Studies in human tissue supporting sequential spread	Cell culture	Animal models
α-synuclein	PD, DLB and MSA	Presynaptic	Cytoplasmic	PD⁸⁰ and MSA¹⁰⁵	39,40,62,177 178	41–44
Amyloid-β	AD	Transmembrane (APP)	Extracellular	AD⁶⁶,⁷¹	179	23,31,180–182
Mutant huntingtin	HD	Nuclear	Nuclear	–	60	–
Mutant superoxide dismutase 1	ALS	Cytoplasmic	Cytoplasmic	–	56	–
RNA-binding protein FUS	ALS and FTLD-FUS	Nuclear	Cytoplasmic	–	–	–
Tau	AD, FTLD-tau (including PiD, PSP and CBD) and CTE	Cytoplasmic	Cytoplasmic	AD⁶⁶ and CTE⁷	50,55	25,183
TDP43	ALS and FTLD-TDP	Nuclear	Cytoplasmic	ALS⁹⁶, FTLD-TDP¹⁰⁴ and AD¹⁰³^*	48,49	–

AD, Alzheimer disease; ALS, amyotrophic lateral sclerosis; APP, amyloid precursor protein (a transmembrane precursor protein whose proteolysis generates amyloid-P); CBD, corticobasal degeneration; CTE, chronic traumatic encephalopathy; DLB, dementia with Lewy bodies; FTLD, frontotemporal lobar degeneration; HD, Huntington disease; MSA, multiple system atrophy; PD, Parkinson disease; PiD, Pick disease; PSP, progressive supranuclear palsy; TDP43, TAR DNA-binding protein 43.

Although AD is primarily characterized by tau and amyloid-P pathology, TDP43 pathology is observed in up to 57% of cases.