SAGE KE Bulletin Board

New Mouse Models for studying the role of apoE in AD

5 March 2006

Dietmar R. Thal

Comment on Van Dooren et al. "Neuronal or glial expression of human apolipoprotein E4 affects parenchymal and vascular amyloid pathology differentially in different brain regions of double- and triple transgenic mice" Am J Pathol 168 (2006) 245-260

Van Dooren et al. (1) report double and triple transgenic mice expressing 1) human apolipoprotein E4 (apoE4) a) driven by a neuron specific Thy1 promotor or b) driven by an astrocyte-specific GFAP- promotor, 2) mutant human APP, and in the event of triple transgenic animals 3) mutant human presenilin 1. The neuronal expression of apoE4 increased Abeta-deposition in the subiculum and in cortical vessels in contrast to glial expressed apoE4 whereas in other regions no differences were reported. These differences in Abeta-deposition may be related to the higher levels of soluble Abeta in animals with neuronal apoE4 expression compared with those expressing glial apoE4. Therefore, mice expressing human Thy1 or GFAP-driven apoE4 without an apoE knockout background are an interesting model to study the effects of brain derived apoE on the deposition of Abeta in comparison to intrinsic mouse apoE produced everywhere in the animal. Interactions between apoE and Abeta appear to influence the initiation of Abeta deposition insofar as the presence of apoE supports Abeta deposition in comparison to apoE knockout mice (2) and insofar as apoE has been reported to occur in distinct types of newly formed senile plaques (3). The mouse models introduced by Van Dooren et al. (1) appear to be a good model system to study the effects of apoE on the initiation of Abeta- deposition as well as the different roles of neurons and glial cells in this process.


1. T. Van Dooren, D. Muyllaert, P. Borghgraef, A. Cresens, H. Devijver, I. Van der Auwera, S. Wera, I. Dewachter, F. Van Leuven, Neuronal or glial expression of human apolipoprotein e4 affects parenchymal and vascular amyloid pathology differentially in different brain regions of double- and triple-transgenic mice. Am J Pathol 168, 245-260 (Jan, 2006).

2. K. R. Bales, T. Verina, R. C. Dodel, Y. Du, L. Altstiel, M. Bender, P. Hyslop, E. M. Johnstone, S. P. Little, D. J. Cummins, P. Piccardo, B. Ghetti, S. M. Paul, Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition. Nat Genet 17, 263-264 (Nov, 1997).

3. D. R. Thal, E. Capetillo-Zarate, C. Schultz, U. Rüb, T. C. Saido, H. Yamaguchi, C. Haass, W. S. T. Griffin, K. Del Tredici, H. Braak, E. Ghebremedhin, Apolipoprotein E co-localizes with newly formed amyloid ß- protein (Aß)-deposits lacking immunoreactivity against N-terminal epitopes of Aß in a genotype-dependent manner. Acta Neuropathol 110, 459- 471 (2005).

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