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Prion-like seeding and nucleation of intracellular amyloid-β

Olsson, Tomas T. LU ; Klementieva, Oxana LU and Gouras, Gunnar K. LU (2018) In Neurobiology of Disease 113. p.1-10
Abstract

Alzheimer's disease (AD) brain tissue can act as a seed to accelerate aggregation of amyloid-β (Aβ) into plaques in AD transgenic mice. Aβ seeds have been hypothesized to accelerate plaque formation in a prion-like manner of templated seeding and intercellular propagation. However, the structure(s) and location(s) of the Aβ seeds remain unknown. Moreover, in contrast to tau and α-synuclein, an in vitro system with prion-like Aβ has not been reported. Here we treat human APP expressing N2a cells with AD transgenic mouse brain extracts to induce inclusions of Aβ in a subset of cells. We isolate cells with induced Aβ inclusions and using immunocytochemistry, western blot and infrared spectroscopy show that these cells produce oligomeric Aβ... (More)

Alzheimer's disease (AD) brain tissue can act as a seed to accelerate aggregation of amyloid-β (Aβ) into plaques in AD transgenic mice. Aβ seeds have been hypothesized to accelerate plaque formation in a prion-like manner of templated seeding and intercellular propagation. However, the structure(s) and location(s) of the Aβ seeds remain unknown. Moreover, in contrast to tau and α-synuclein, an in vitro system with prion-like Aβ has not been reported. Here we treat human APP expressing N2a cells with AD transgenic mouse brain extracts to induce inclusions of Aβ in a subset of cells. We isolate cells with induced Aβ inclusions and using immunocytochemistry, western blot and infrared spectroscopy show that these cells produce oligomeric Aβ over multiple replicative generations. Further, we demonstrate that cell lysates of clones with induced oligomeric Aβ can induce aggregation in previously untreated N2a APP cells. These data strengthen the case that Aβ acts as a prion-like protein, demonstrate that Aβ seeds can be intracellular oligomers and for the first time provide a cellular model of nucleated seeding of Aβ.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, Amyloid, FTIR, Oligomers, Prion-like
in
Neurobiology of Disease
volume
113
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:85041482622
ISSN
0969-9961
DOI
10.1016/j.nbd.2018.01.015
language
English
LU publication?
yes
id
de990b68-e871-4eaf-8cdf-83261b459187
date added to LUP
2018-02-20 08:50:05
date last changed
2018-05-29 10:31:28
@article{de990b68-e871-4eaf-8cdf-83261b459187,
  abstract     = {<p>Alzheimer's disease (AD) brain tissue can act as a seed to accelerate aggregation of amyloid-β (Aβ) into plaques in AD transgenic mice. Aβ seeds have been hypothesized to accelerate plaque formation in a prion-like manner of templated seeding and intercellular propagation. However, the structure(s) and location(s) of the Aβ seeds remain unknown. Moreover, in contrast to tau and α-synuclein, an in vitro system with prion-like Aβ has not been reported. Here we treat human APP expressing N2a cells with AD transgenic mouse brain extracts to induce inclusions of Aβ in a subset of cells. We isolate cells with induced Aβ inclusions and using immunocytochemistry, western blot and infrared spectroscopy show that these cells produce oligomeric Aβ over multiple replicative generations. Further, we demonstrate that cell lysates of clones with induced oligomeric Aβ can induce aggregation in previously untreated N2a APP cells. These data strengthen the case that Aβ acts as a prion-like protein, demonstrate that Aβ seeds can be intracellular oligomers and for the first time provide a cellular model of nucleated seeding of Aβ.</p>},
  author       = {Olsson, Tomas T. and Klementieva, Oxana and Gouras, Gunnar K.},
  issn         = {0969-9961},
  keyword      = {Alzheimer's disease,Amyloid,FTIR,Oligomers,Prion-like},
  language     = {eng},
  month        = {05},
  pages        = {1--10},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {Prion-like seeding and nucleation of intracellular amyloid-β},
  url          = {http://dx.doi.org/10.1016/j.nbd.2018.01.015},
  volume       = {113},
  year         = {2018},
}