title: β-Amyloid is transmitted via neuronal connections along axonal membranes.
abstract: OBJECTIVE
  β-amyloid plaque is a critical pathological feature of Alzheimer disease. Pathologic studies suggest that neurodegeneration may occur in a retrograde fashion from axon terminals near β-amyloid plaques, and that plaque may spread through brain regions. However, there is no direct experimental evidence to show transmission of β-amyloid.
  
  
  METHODS
  Microscopic imaging data of β-amyloid transmission was acquired in cortical neuron cultures from Sprague-Dawley rat embryos using polydimethylsiloxane (PDMS) microfluidic culture chambers and in brain sections from in vivo β-amyloid injection.
  
  
  RESULTS
  We present direct imaging evidence in cultured cortical neurons, using PDMS microfluidic culture chambers, that β-amyloid is readily absorbed by axonal processes and retrogradely transported to neuronal cell bodies. Transmission of β-amyloid via neuronal connections was also confirmed in mouse brain. β-Amyloid absorbed by distal axons accumulates in axonal swellings, mitochondria, and lysosomes of the cell bodies. Interestingly, dynasore, an inhibitor of dynamin, which is a protein indispensable for endocytosis, did not prevent retrograde transport of β-amyloid, indicating that β-amyloid is absorbed onto axonal membranes and transmitted via them to the cell body. Dynasore did decrease the transneuronal transmission of β-amyloid, suggesting that this requires the internalization and secretion of β-amyloid.
  
  
  CONCLUSIONS
  Our findings provide direct in vitro and in vivo evidence for spreading of β-amyloid through neuronal connections, and suggest possible therapeutic approaches to blocking this spread.
authors.affiliation: Alzheimer's Disease Experts Laboratory, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul, Korea; Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Seoul, Korea; Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Ha-Lim
authors.initials: HL
authors.lastname: Song
authors.forename: Sungbo
authors.initials: S
authors.lastname: Shim
authors.forename: Dong-Hou
authors.initials: DH
authors.lastname: Kim
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Won
authors.forename: Segyeong
authors.initials: S
authors.lastname: Joo
authors.forename: Sudong
authors.initials: S
authors.lastname: Kim
authors.forename: Noo Li
authors.initials: NL
authors.lastname: Jeon
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Yoon
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004129:Dimethylpolysiloxanes / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D061251:Primary Cell Culture; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D004129:Dimethylpolysiloxanes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C528539:poly(dimethyldiphenylsiloxane)