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

Direct link
Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer's disease cases
Show others and affiliations
2010 (English)In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 117, no 1, 85-96 p.Article in journal (Refereed) Published
Abstract [en]

The presence of Abeta(pE3) (N-terminal truncated Abeta starting with pyroglutamate) in Alzheimer's disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of Abeta peptides in senile plaques of AD brains. This was later confirmed by other reports investigating AD and Down's syndrome postmortem brain tissue. Importantly, Abeta(pE3) has a higher aggregation propensity, and stability, and shows an increased toxicity compared to full-length Abeta. We have recently shown that intraneuronal accumulation of Abeta(pE3) peptides induces a severe neuron loss and an associated neurological phenotype in the TBA2 mouse model for AD. Given the increasing interest in Abeta(pE3), we have generated two novel monoclonal antibodies which were characterized as highly specific for Abeta(pE3) peptides and herein used to analyze plaque deposition in APP/PS1KI mice, an AD model with severe neuron loss and learning deficits. This was compared with the plaque pattern present in brain tissue from sporadic and familial AD cases. Abundant plaques positive for Abeta(pE3) were present in patients with sporadic AD and familial AD including those carrying mutations in APP (arctic and Swedish) and PS1. Interestingly, in APP/PS1KI mice we observed a continuous increase in Abeta(pE3) plaque load with increasing age, while the density for Abeta(1-x ) plaques declined with aging. We therefore assume that, in particular, the peptides starting with position 1 of Abeta are N-truncated as disease progresses, and that, Abeta(pE3) positive plaques are resistant to age-dependent degradation likely due to their high stability and propensity to aggregate.

Place, publisher, year, edition, pages
2010. Vol. 117, no 1, 85-96 p.
Keyword [en]
Transgenic mice, Arctic mutation, Swedish mutation, Presenilin-1 mutation, Sporadic Alzheimer's disease, Pyroglutamate Abeta, Biacore, Antibody specificity
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-123003DOI: 10.1007/s00702-009-0314-xISI: 000272464800012PubMedID: 19823761OAI: oai:DiVA.org:uu-123003DiVA: diva2:311596
Available from: 2010-04-22 Created: 2010-04-22 Last updated: 2010-06-21Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
In the same journal
Journal of neural transmission
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 134 hits
ReferencesLink to record
Permanent link

Direct link