Preparing your results

Our searching services are busy right now. You're search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Selective hippocampal neurodegeneration in transgenic mice expressing small amounts of truncated Aβ is induced by pyroglutamate-Aβ formation.

Posttranslational amyloid-β (Aβ) modification is considered to play an important role in Alzheimer's disease (AD) etiology. An N-terminally modified Aβ species, pyroglutamate-amyloid-β (pE3-Aβ), has been described as a major constituent of Aβ deposits specific to human AD but absent in normal aging. Formed via cyclization of truncated Aβ species by glutaminyl cyclase (QC; QPCT) and/or its isoenzyme (isoQC; QPCTL), pE3-Aβ aggregates rapidly and is known to seed additional Aβ aggregation. To directly investigate pE3-Aβ toxicity in vivo, we generated and characterized transgenic TBA2.1 and TBA2.2 mice, which express truncated mutant human Aβ. Along with a rapidly developing behavioral phenotype, these mice showed progressively accumulating Aβ and pE3-Aβ deposits in brain regions of neuronal loss, impaired long-term potentiation, microglial activation, and astrocytosis. Illustrating a threshold for pE3-Aβ neurotoxicity, this phenotype was not found in heterozygous animals but in homozygous TBA2.1 or double-heterozygous TBA2.1/2.2 animals only. A significant amount of pE3-Aβ formation was shown to be QC-dependent, because crossbreeding of TBA2.1 with QC knock-out, but not isoQC knock-out, mice significantly reduced pE3-Aβ levels. Hence, lowering the rate of QC-dependent posttranslational pE3-Aβ formation can, in turn, lower the amount of neurotoxic Aβ species in AD.

Pubmed ID: 21900558


  • Alexandru A
  • Jagla W
  • Graubner S
  • Becker A
  • Bäuscher C
  • Kohlmann S
  • Sedlmeier R
  • Raber KA
  • Cynis H
  • Rönicke R
  • Reymann KG
  • Petrasch-Parwez E
  • Hartlage-Rübsamen M
  • Waniek A
  • Rossner S
  • Schilling S
  • Osmand AP
  • Demuth HU
  • von Hörsten S


The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

September 7, 2011

Associated Grants


Mesh Terms

  • Aging
  • Alzheimer Disease
  • Amyloid beta-Protein Precursor
  • Animals
  • Behavior, Animal
  • Brain
  • Enzyme-Linked Immunosorbent Assay
  • Gliosis
  • Heredodegenerative Disorders, Nervous System
  • Hippocampus
  • Humans
  • Immunohistochemistry
  • Kinetics
  • Long-Term Potentiation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Microscopy, Electron
  • Neuronal Plasticity
  • Phenotype
  • Postural Balance
  • Protein Processing, Post-Translational
  • Pyrrolidonecarboxylic Acid
  • Reflex, Startle
  • Reverse Transcriptase Polymerase Chain Reaction