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Prion-like seeding ...
Prion-like seeding and nucleation of intracellular amyloid-β
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- Olsson, Tomas T. (författare)
- Lund University,Lunds universitet,Experimentell demensforskning,Forskargrupper vid Lunds universitet,Experimental Dementia Research,Lund University Research Groups
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- Klementieva, Oxana (författare)
- Lund University,Lunds universitet,Experimentell demensforskning,Forskargrupper vid Lunds universitet,Medicinsk mikrospektroskopi,Experimental Dementia Research,Lund University Research Groups,Medical Microspectroscopy
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- Gouras, Gunnar K. (författare)
- Lund University,Lunds universitet,Experimentell demensforskning,Forskargrupper vid Lunds universitet,Experimental Dementia Research,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- Engelska 10 s.
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 113, s. 1-10
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Nyckelord
- Alzheimer's disease
- Amyloid
- FTIR
- Oligomers
- Prion-like
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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