PMID- 26344875
OWN - NLM
STAT- MEDLINE
DCOM- 20160607
LR  - 20150908
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Linking)
VI  - 36
IP  - 10
DP  - 2015 Oct
TI  - Neurofilament light gene deletion exacerbates amyloid, dystrophic neurite, and 
      synaptic pathology in the APP/PS1 transgenic model of Alzheimer's disease.
PG  - 2757-67
LID - S0197-4580(15)00359-0 [pii]
LID - 10.1016/j.neurobiolaging.2015.07.003 [doi]
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease associated 
      with the loss of cognitive function. Neurofilament (NF) triplet proteins, the 
      major structural (intermediate filament) proteins of neurons, are expressed in a 
      subset of pyramidal cells that show a high degree of vulnerability to 
      degeneration in AD. Alterations in the NF triplet proteins in amyloid-beta (Abeta) 
      plaque-associated dystrophic neurites (DNs) represent the first cytoskeletal 
      aberration to occur in the neocortex in the earliest stages of AD. We generated 
      transgenic APP/PS1 (APPswe/PSEN1dE9) mice on the neurofilament light knockout 
      (NFL KO) background to explore the role of NFL deletion in the context of DN 
      formation, synaptic changes, and other neuropathologic features. Our analysis 
      demonstrated that NFL deficiency significantly increased neocortical DN 
      pathology, Abeta deposition, synapse vulnerability, and microgliosis in APP/PS1 
      mice. Thus, NFs may have a role in protecting neurites from dystrophy and in 
      regulating cellular pathways related to the generation of Abeta plaques.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Fernandez-Martos, Carmen M
AU  - Fernandez-Martos CM
AD  - Wicking Dementia Research and Education Centre, Faculty of Health, University of 
      Tasmania, Hobart, Tasmania, Australia. Electronic address: 
      Carmen.Fernandezmartos@utas.edu.au.
FAU - King, Anna E
AU  - King AE
AD  - Wicking Dementia Research and Education Centre, Faculty of Health, University of 
      Tasmania, Hobart, Tasmania, Australia.
FAU - Atkinson, Rachel A K
AU  - Atkinson RA
AD  - Wicking Dementia Research and Education Centre, Faculty of Health, University of 
      Tasmania, Hobart, Tasmania, Australia.
FAU - Woodhouse, Adele
AU  - Woodhouse A
AD  - Wicking Dementia Research and Education Centre, Faculty of Health, University of 
      Tasmania, Hobart, Tasmania, Australia.
FAU - Vickers, James C
AU  - Vickers JC
AD  - Wicking Dementia Research and Education Centre, Faculty of Health, University of 
      Tasmania, Hobart, Tasmania, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150710
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Neurofilament Proteins)
RN  - 0 (neurofilament protein L)
SB  - IM
MH  - Alzheimer Disease/*genetics/*pathology
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - *Gene Deletion
MH  - Hippocampus/metabolism
MH  - Mice, Transgenic
MH  - Microglia/pathology
MH  - Neocortex/metabolism
MH  - Neurites/*metabolism/*pathology
MH  - Neurofilament Proteins/*genetics
MH  - Plaque, Amyloid/genetics/metabolism
MH  - Synapses/*pathology
OTO - NOTNLM
OT  - Alzheimer's disease (AD)
OT  - Dystrophic neurites (DNs)
OT  - NF light (NEFL) gene knockout
OT  - Neurofilaments (NFs)
EDAT- 2015/09/08 06:00
MHDA- 2016/06/09 06:00
CRDT- 2015/09/08 06:00
PHST- 2015/01/29 00:00 [received]
PHST- 2015/07/02 00:00 [revised]
PHST- 2015/07/02 00:00 [accepted]
PHST- 2015/09/08 06:00 [entrez]
PHST- 2015/09/08 06:00 [pubmed]
PHST- 2016/06/09 06:00 [medline]
AID - S0197-4580(15)00359-0 [pii]
AID - 10.1016/j.neurobiolaging.2015.07.003 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2015 Oct;36(10):2757-67. doi: 
      10.1016/j.neurobiolaging.2015.07.003. Epub 2015 Jul 10.