No alterations of hippocampal neuronal number and synaptic bouton number in a transgenic mouse model expressing the beta-cleaved C-terminal APP fragment

Publication

No alterations of hippocampal neuronal number and synaptic bouton number in a transgenic mouse model expressing the beta-cleaved C-terminal APP fragment

Journal Paper/Review - Mar 1, 2003

Rutten Bart P F, Bayer Thomas A, Multhaup Gerd, Beyreuther Konrad, Korr Hubert, Steinbusch Harry W M, Vehoff Jochen, Lichtenthaler Stefan F, Van de Berg Wilma D J, Wirths Oliver, Schmitz Christoph

Units

Neurologie

PubMed

12667466

Citation

Rutten B, Bayer T, Multhaup G, Beyreuther K, Korr H, Steinbusch H, Vehoff J, Lichtenthaler S, Van de Berg W, Wirths O, Schmitz C. No alterations of hippocampal neuronal number and synaptic bouton number in a transgenic mouse model expressing the beta-cleaved C-terminal APP fragment. Neurobiology of disease 2003; 12:110-20.

Type

Journal Paper/Review (English)

Journal

Neurobiology of disease 2003; 12

Publication Date

Mar 1, 2003

Issn Print

0969-9961

Pages

110-20

Brief description/objective

Previous studies in the literature have resulted in conflicting reports on the potential neurotoxicity of the beta-cleaved Alzheimer's disease C-terminal fragment (beta-CTF) of beta-amyloid precursor protein in vivo. To readdress this question by rigorous quantitative methods, we analyzed transgenic mice expressing human beta-CTF with the I45F mutation (SPA4CT) under control of the prion protein promoter by stereological techniques. The transgene was expressed in hippocampus and cortex in large pyramidal neurons and in dentate gyrus granule cells. Proteolytic processing of beta-CTF released Abeta. However, most of it remained uncleaved. Neurodegeneration was evaluated by investigating the numbers of hippocampal pyramidal and granule neurons, as well as the number of synaptophysin-immunopositive presynaptic boutons in the hippocampus of 15-month-old SPA4CT mice with design-based stereological techniques. The analyses showed that a fourfold higher expression of the transgene compared to murine APP levels had no effect on the numbers of both neurons and synaptophysin-immunopositive presynaptic boutons. These data implicate that expression of beta-CTF per se is not neurotoxic, and that other mechanisms are responsible for the neurotoxic events in Alzheimer's disease brain.