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
Observations in APP bitransgenic mice suggest that diffuse and compact plaques form via independent processes in Alzheimer's disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. (Molekylär geriatrik)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. (Molekylär geriatrik)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Show others and affiliations
2011 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 178, no 5, 2286-2298 p.Article in journal (Refereed) Published
Abstract [en]

Studies of familial Alzheimer's disease suggest that misfolding and aggregation of amyloid-β (Aβ) peptides initiate the pathogenesis. The Arctic mutation of Aβ precursor protein (APP) results in AD, and Arctic Aβ is more prone to form Aβ protofibrils and extracellular deposits. Herein is demonstrated that the burden of diffuse Aβ deposits but not compact plaques is increased when tg-Swe mice are crossed with tg-ArcSwe mice synthesizing low levels of Arctic Aβ. The diffuse deposits in bitransgenic mice, which contain primarily wild-type Aβ42, accumulate in regions both with and without transgene expression. However, APP processing, when compared with tg-Swe, remains unchanged in young bitransgenic mice, whereas wild-type Aβ42 aggregation is accelerated and fibril architecture is altered in vitro and in vivo when a low level of Arctic Aβ42 is introduced. Thus, the increased number of diffuse deposits is likely due to physical interactions between Arctic Aβ and wild-type Aβ42. The selective increase of a single type of parenchymal Aβ deposit suggests that different pathways lead to formation of diffuse and compact plaques. These findings could have general implications for Alzheimer's disease pathogenesis and particular relevance to patients heterozygous for the Arctic APP mutation. Moreover, it further illustrates how Aβ neuropathologic features can be manipulated in vivo by mechanisms similar to those originally conceptualized in prion research.

Place, publisher, year, edition, pages
2011. Vol. 178, no 5, 2286-2298 p.
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-165029DOI: 10.1016/j.ajpath.2011.01.052ISI: 000298306800034PubMedID: 21514441OAI: oai:DiVA.org:uu-165029DiVA: diva2:471349
Available from: 2012-01-02 Created: 2012-01-02 Last updated: 2017-12-08Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Lord, AnnaWestermark, GunillaNilsson, Lars N G

Search in DiVA

By author/editor
Lord, AnnaWestermark, GunillaNilsson, Lars N G
By organisation
GeriatricsDepartment of Medical Cell Biology
In the same journal
American Journal of Pathology
Neurosciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 627 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