PMID- 26293809
OWN - NLM
STAT- MEDLINE
DCOM- 20160421
LR  - 20181113
IS  - 2051-5960 (Electronic)
IS  - 2051-5960 (Linking)
VI  - 3
DP  - 2015 Aug 21
TI  - Intracellular amyloid beta oligomers impair organelle transport and induce dendritic 
      spine loss in primary neurons.
PG  - 51
LID - 10.1186/s40478-015-0230-2 [doi]
LID - 51
AB  - INTRODUCTION: Synaptic dysfunction and intracellular transport defects are early 
      events in Alzheimer's disease (AD). Extracellular amyloid beta (Abeta) oligomers cause 
      spine alterations and impede the transport of proteins and organelles such as 
      brain-derived neurotrophic factor (BDNF) and mitochondria that are required for 
      synaptic function. Meanwhile, intraneuronal accumulation of Abeta precedes its 
      extracellular deposition and is also associated with synaptic dysfunction in AD. 
      However, the links between intracellular Abeta, spine alteration, and mechanisms 
      that support synaptic maintenance such as organelle trafficking are poorly 
      understood. RESULTS: We compared the effects of wild-type and Osaka 
      (E693Delta)-mutant amyloid precursor proteins: the former secretes Abeta into 
      extracellular space and the latter accumulates Abeta oligomers within cells. First 
      we investigated the effects of intracellular Abeta oligomers on dendritic spines in 
      primary neurons and their tau-dependency using tau knockout neurons. We found 
      that intracellular Abeta oligomers caused a reduction in mushroom, or mature spines, 
      independently of tau. We also found that intracellular Abeta oligomers significantly 
      impaired the intracellular transport of BDNF, mitochondria, and recycling 
      endosomes: cargoes essential for synaptic maintenance. A reduction in BDNF 
      transport by intracellular Abeta oligomers was also observed in tau knockout 
      neurons. CONCLUSIONS: Our findings indicate that intracellular Abeta oligomers 
      likely contribute to early synaptic pathology in AD and argue against the 
      consensus that Abeta-induced spine loss and transport defects require tau.
FAU - Umeda, Tomohiro
AU  - Umeda T
AD  - Department of Neuroscience, Osaka City University Graduate School of Medicine, 
      1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
AD  - Core Research for Evolutional Science and Technology, Japan Science and 
      Technology Agency, Kawaguchi, Japan.
FAU - Ramser, Elisa M
AU  - Ramser EM
AD  - Department of Biological Sciences, Simon Fraser University, Burnaby, British 
      Columbia, V5A 1S6, Canada.
FAU - Yamashita, Minato
AU  - Yamashita M
AD  - Department of Neuroscience, Osaka City University Graduate School of Medicine, 
      1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
FAU - Nakajima, Koichi
AU  - Nakajima K
AD  - Department of Immunology, Osaka City University Graduate School of Medicine, 
      Osaka, Japan.
FAU - Mori, Hiroshi
AU  - Mori H
AD  - Core Research for Evolutional Science and Technology, Japan Science and 
      Technology Agency, Kawaguchi, Japan.
AD  - Department of Clinical Neuroscience, Osaka City University Medical School, Osaka, 
      Japan.
FAU - Silverman, Michael A
AU  - Silverman MA
AD  - Department of Biological Sciences, Simon Fraser University, Burnaby, British 
      Columbia, V5A 1S6, Canada. masilver@sfu.ca.
FAU - Tomiyama, Takami
AU  - Tomiyama T
AD  - Department of Neuroscience, Osaka City University Graduate School of Medicine, 
      1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan. tomi@med.osaka-cu.ac.jp.
AD  - Core Research for Evolutional Science and Technology, Japan Science and 
      Technology Agency, Kawaguchi, Japan. tomi@med.osaka-cu.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150821
PL  - England
TA  - Acta Neuropathol Commun
JT  - Acta neuropathologica communications
JID - 101610673
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Mapt protein, mouse)
RN  - 0 (enhanced green fluorescent protein)
RN  - 0 (tau Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
EIN - Acta Neuropathol Commun. 2016;4:7. PMID: 26822851
MH  - Amyloid beta-Peptides/*metabolism/pharmacology
MH  - Amyloid beta-Protein Precursor/genetics
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cells, Cultured
MH  - Dendritic Spines/*pathology
MH  - Dose-Response Relationship, Drug
MH  - Embryo, Mammalian
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Hippocampus/cytology
MH  - Intracellular Fluid/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutation/genetics
MH  - Neurons/*ultrastructure
MH  - Organelles/*metabolism
MH  - Protein Transport/*physiology
MH  - Transfection
MH  - tau Proteins/deficiency/genetics
PMC - PMC4546183
EDAT- 2015/08/22 06:00
MHDA- 2016/04/22 06:00
PMCR- 2015/08/21
CRDT- 2015/08/22 06:00
PHST- 2015/07/03 00:00 [received]
PHST- 2015/08/09 00:00 [accepted]
PHST- 2015/08/22 06:00 [entrez]
PHST- 2015/08/22 06:00 [pubmed]
PHST- 2016/04/22 06:00 [medline]
PHST- 2015/08/21 00:00 [pmc-release]
AID - 10.1186/s40478-015-0230-2 [pii]
AID - 230 [pii]
AID - 10.1186/s40478-015-0230-2 [doi]
PST - epublish
SO  - Acta Neuropathol Commun. 2015 Aug 21;3:51. doi: 10.1186/s40478-015-0230-2.