uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Serial propagation of distinct strains of A beta prions from Alzheimer's disease patients
Show others and affiliations
2014 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, no 28, 10323-10328 p.Article in journal (Refereed) Published
Abstract [en]

An increasing number of studies argues that self-propagating protein conformations (i.e., prions) feature in the pathogenesis of several common neurodegenerative diseases. Mounting evidence contends that aggregates of the amyloid-beta (A beta) peptide become self-propagating in Alzheimer's disease (AD) patients. An important characteristic of prions is their ability to replicate distinct strains, the biological information for which is enciphered within different conformations of protein aggregates. To investigate whether distinct strains of A beta prions can be discerned in AD patients, we performed transmission studies in susceptible transgenic mice using brain homogenates from sporadic or heritable (Arctic and Swedish) AD cases. Mice inoculated with the Arctic AD sample exhibited a pathology that could be distinguished from mice inoculated with the Swedish or sporadic AD samples, which was judged by differential accumulation of A beta isoforms and the morphology of cerebrovascular A beta deposition. Unlike Swedish AD- or sporadic AD-inoculated animals, Arctic AD-inoculated mice, like Arctic AD patients, displayed a prominent A beta 38-containing cerebral amyloid angiopathy. The divergent transmission behavior of the Arctic AD sample compared with the Swedish and sporadic AD samples was maintained during second passage in mice, showing that A beta strains are serially transmissible. We conclude that at least two distinct strains of A beta prions can be discerned in the brains of AD patients and that strain fidelity was preserved on serial passage in mice. Our results provide a potential explanation for the clinical and pathological heterogeneity observed in AD patients.

Place, publisher, year, edition, pages
2014. Vol. 111, no 28, 10323-10328 p.
Keyword [en]
neurodegeneration, bioluminescence imaging, seeding, proteinopathies
National Category
Geriatrics
Identifiers
URN: urn:nbn:se:uu:diva-230093DOI: 10.1073/pnas.1408900111ISI: 000338985700067PubMedID: 24982139OAI: oai:DiVA.org:uu-230093DiVA: diva2:742849
Available from: 2014-09-02 Created: 2014-08-19 Last updated: 2017-12-05Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Lannfelt, LarsIngelsson, Martin

Search in DiVA

By author/editor
Lannfelt, LarsIngelsson, Martin
By organisation
Geriatrics
In the same journal
Proceedings of the National Academy of Sciences of the United States of America
Geriatrics

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 902 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf