Brain Advance Access published online on July 14, 2006
Brain, doi:10.1093/brain/awl176
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1 Department of Neuropathlogy, University of Bonn, Bonn, Germany
* To whom correspondence should be addressed. The amyloid
Received February 28, 2006
Revised April 20, 2006
Accepted June 7, 2006
Article
Selective vulnerability of different types of commissural neurons for amyloid
Estibaliz Capetillo-Zarate 1,
Matthias Staufenbiel 2,
Dorothee Abramowski 2,
Christian Haass 3,
Angelika Escher 4,
Christine Stadelmann 4,
Haruyasu Yamaguchi 5,
Otmar D. Wiestler 6,
and
Dietmar Rudolf Thal 1 *
-protein-induced neurodegeneration in APP23 mice correlates with dendritic tree morphology
2 Novartis Institutes for Biomedical Research Basel, Basel, Switzerland
3 Department of Biochemistry, Adolf-Butenandt Institute, Ludwig Maximilians University, Munich, Germany
4 Department of Neuropathology, Georg-August University, Göttingen, Germany
5 Gunma University School of Health Sciences, Maebashi, Gunma, Japan
6 Department of Neuropathlogy, University of Bonn, Bonn, Germany; Present address: DKFZ-German Cancer Research Center, D-69120 Heidelberg, Germany
Dietmar Rudolf Thal, E-mail: Dietmar.Thal{at}uni-bonn.de
Abstract 
-protein (A) is the main component of Alzheimer's disease-related senile plaques. Although A is associated with the development of Alzheimer's disease, it has not been shown which forms of A induce neurodegeneration in vivo and which types of neurons are vulnerable. To address these questions, we implanted DiI crystals into the left frontocentral cortex of APP23 transgenic mice overexpressing mutant human APP (amyloid precursor protein gene) and of littermate controls. Traced commissural neurons in layer III of the right frontocentral cortex were quantified in 3-, 5-, 11- and 15-month-old mice. Three different types of commissural neurons were traced. At 3 months of age no differences in the number of labelled commissural neurons were seen in APP23 mice compared with wild-type mice. A selective reduction of the heavily ramified type of neurons was observed in APP23 mice compared with wild-type animals at 5, 11 and 15 months of age, starting when the first A-deposits occurred in the frontocentral cortex at 5 months. The other two types of commissural neurons did not show alterations at 5 and 11 months. At 15 months, the number of traced sparsely ramified pyramidal neurons was reduced in addition to that of the heavily ramified neurons in APP23 mice compared with wild-type mice. At this time A-deposits were seen in the neo- and allocortex as well as in the basal ganglia and the thalamus. In summary, our results show that A induces progressive degeneration of distinct types of commissural neurons. Degeneration of the most vulnerable neurons starts in parallel with the occurrence of the first fibrillar A-deposits in the neocortex, that is, with the detection of aggregated A. The involvement of additional neuronal subpopulations is associated with the expansion of A-deposition into further brain regions. The vulnerability of different types of neurons to A, thereby, is presumably related to the complexity of their dendritic morphology.
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