Affiliations: Division of Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University Medicine Göttingen, Georg-August-University of Göttingen, Germany
Correspondence:
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Correspondence to: Dr. rer. nat. Thomas A. Bayer, Division of Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University Medicine Göttingen, von-Siebold-Strasse 5, 37075 Göttingen, Germany. Tel.: +49 551 39 22912; Fax: +49 551 39 10291; E-mail: [email protected].
Abstract: Pyroglutamate-modified amyloid-β (Aβ) at amino acid position three (AβpE3–42) is gaining considerable attention as a potential key player in the pathogenesis of Alzheimer's disease (AD). AβpE3–42 is abundant in AD brain and has a high aggregation propensity, stability, and cellular toxicity. The aim of the present work was to study the effect of AβpE3–42 expression on neuron loss and associated behavioral deficits using the TBA42 transgenic mouse model. Expression of pyroglutamate Aβ3–42 triggers hippocampal CA1 neuron loss and behavioral deficits in the TBA42 mouse model. Mice elicited significant neuron death (−35% at the age of 12 months), deficits in the spatial reference memory, working memory, loss of anxiety, and severe motor deficits in an age-dependent manner. These results support a major pathological function of pyroglutamate Aβ in AD.
Keywords: Hippocampus, motor deficits, N-truncated Aβ, spatial reference memory, stereology, transgenic mouse model, working memory
