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Transgenic BACE expression in mouse neurons accelerates amyloid plaque pathology.
J Neural Transm (Vienna) 2004; 111(3):413-25JN

Abstract

The cleavage of APP by BACE initiates the amyloidogenic process in Alzheimer's disease (AD). We have generated transgenic mice expressing BACE and double transgenic mice expressing BACE and the Swedish mutations of APP (SwAPP) in neurons. BACE transgenic mice did not develop beta-amyloid plaques by age of 14 months, but showed intracellular beta-amyloid immunoreactivity that was co-localized with transgenic BACE in neurons. Abeta levels were increased and AD-like pathology was accelerated in double transgenic mice expressing both BACE and SwAPP. At two months of age, early signs of extracellular Abeta deposition and reactive astrocytes were found in double transgenic, but not in single transgenic mice. Furthermore, at four months, well defined beta-amyloid deposits surrounded by activated astrocytes could be detected in the double transgenic mice. We suggest that BACE overexpression is not sufficient to produce beta-amyloid plaques, but simultaneous expression of BACE and its substrate (SwAPP) leads to an accelerated amyloid plaque formation.

Authors+Show Affiliations

Division of Psychiatry Research, University of Zurich, Zurich, Switzerland. mohajeri@bli.unizh.chNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14991462

Citation

Mohajeri, M H., et al. "Transgenic BACE Expression in Mouse Neurons Accelerates Amyloid Plaque Pathology." Journal of Neural Transmission (Vienna, Austria : 1996), vol. 111, no. 3, 2004, pp. 413-25.
Mohajeri MH, Saini KD, Nitsch RM. Transgenic BACE expression in mouse neurons accelerates amyloid plaque pathology. J Neural Transm (Vienna). 2004;111(3):413-25.
Mohajeri, M. H., Saini, K. D., & Nitsch, R. M. (2004). Transgenic BACE expression in mouse neurons accelerates amyloid plaque pathology. Journal of Neural Transmission (Vienna, Austria : 1996), 111(3), pp. 413-25.
Mohajeri MH, Saini KD, Nitsch RM. Transgenic BACE Expression in Mouse Neurons Accelerates Amyloid Plaque Pathology. J Neural Transm (Vienna). 2004;111(3):413-25. PubMed PMID: 14991462.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transgenic BACE expression in mouse neurons accelerates amyloid plaque pathology. AU - Mohajeri,M H, AU - Saini,K D, AU - Nitsch,R M, Y1 - 2003/12/03/ PY - 2003/07/03/received PY - 2003/09/03/accepted PY - 2004/3/3/pubmed PY - 2004/6/2/medline PY - 2004/3/3/entrez SP - 413 EP - 25 JF - Journal of neural transmission (Vienna, Austria : 1996) JO - J Neural Transm (Vienna) VL - 111 IS - 3 N2 - The cleavage of APP by BACE initiates the amyloidogenic process in Alzheimer's disease (AD). We have generated transgenic mice expressing BACE and double transgenic mice expressing BACE and the Swedish mutations of APP (SwAPP) in neurons. BACE transgenic mice did not develop beta-amyloid plaques by age of 14 months, but showed intracellular beta-amyloid immunoreactivity that was co-localized with transgenic BACE in neurons. Abeta levels were increased and AD-like pathology was accelerated in double transgenic mice expressing both BACE and SwAPP. At two months of age, early signs of extracellular Abeta deposition and reactive astrocytes were found in double transgenic, but not in single transgenic mice. Furthermore, at four months, well defined beta-amyloid deposits surrounded by activated astrocytes could be detected in the double transgenic mice. We suggest that BACE overexpression is not sufficient to produce beta-amyloid plaques, but simultaneous expression of BACE and its substrate (SwAPP) leads to an accelerated amyloid plaque formation. SN - 0300-9564 UR - https://www.unboundmedicine.com/medline/citation/14991462/Transgenic_BACE_expression_in_mouse_neurons_accelerates_amyloid_plaque_pathology_ L2 - https://dx.doi.org/10.1007/s00702-003-0057-z DB - PRIME DP - Unbound Medicine ER -