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Genetic background regulates beta-amyloid precursor protein processing and beta-amyloid deposition in the mouse.
Hum Mol Genet. 2003 Nov 15; 12(22):2949-56.HM

Abstract

Alzheimer's disease (AD) is a multigenic neurodegenerative disorder characterized by distinct neuropathological hallmarks including deposits of the beta-amyloid (A beta) peptide. A beta is a 39- to 43-amino acid peptide derived from the proteolytic processing of the amyloid precursor protein (APP). While increasing evidence suggests that altered APP processing and A beta metabolism is a common feature of AD, the relationship between the levels of A beta and various APP products and the onset of AD remains unclear. We have undertaken a screen to characterize genetic factors that modify APP processing, A beta metabolism and A beta deposition in a genomic-based yeast artificial chromosome (YAC) transgenic mouse model of AD. A mutant human APP YAC transgene was transferred to three inbred mouse strains. Despite similar levels of holo-APP expression in the congenic strains, the levels of APP C-terminal fragments as well as brain and plasma A beta in young animals varied by genetic background. Furthermore, we demonstrate that age-dependent A beta deposition in the APP YAC transgenic model is dramatically altered depending on the congenic strain examined. These studies demonstrate that APP processing, A beta metabolism and A beta deposition are regulated by genetic background and that analysis of these phenotypes in mice should provide new insights into the factors that regulate AD pathogenesis.

Authors+Show Affiliations

Department of Genetics, Case Western Reserve University, and Center for Human Genetics, University Hospitals of Cleveland, OH 44106-4955, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14506131

Citation

Lehman, Emily J H., et al. "Genetic Background Regulates Beta-amyloid Precursor Protein Processing and Beta-amyloid Deposition in the Mouse." Human Molecular Genetics, vol. 12, no. 22, 2003, pp. 2949-56.
Lehman EJ, Kulnane LS, Gao Y, et al. Genetic background regulates beta-amyloid precursor protein processing and beta-amyloid deposition in the mouse. Hum Mol Genet. 2003;12(22):2949-56.
Lehman, E. J., Kulnane, L. S., Gao, Y., Petriello, M. C., Pimpis, K. M., Younkin, L., Dolios, G., Wang, R., Younkin, S. G., & Lamb, B. T. (2003). Genetic background regulates beta-amyloid precursor protein processing and beta-amyloid deposition in the mouse. Human Molecular Genetics, 12(22), 2949-56.
Lehman EJ, et al. Genetic Background Regulates Beta-amyloid Precursor Protein Processing and Beta-amyloid Deposition in the Mouse. Hum Mol Genet. 2003 Nov 15;12(22):2949-56. PubMed PMID: 14506131.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic background regulates beta-amyloid precursor protein processing and beta-amyloid deposition in the mouse. AU - Lehman,Emily J H, AU - Kulnane,Laura Shapiro, AU - Gao,Yuan, AU - Petriello,Michelle C, AU - Pimpis,Karen M, AU - Younkin,Linda, AU - Dolios,Georgia, AU - Wang,Rong, AU - Younkin,Steven G, AU - Lamb,Bruce T, Y1 - 2003/09/23/ PY - 2003/9/25/pubmed PY - 2004/7/9/medline PY - 2003/9/25/entrez SP - 2949 EP - 56 JF - Human molecular genetics JO - Hum. Mol. Genet. VL - 12 IS - 22 N2 - Alzheimer's disease (AD) is a multigenic neurodegenerative disorder characterized by distinct neuropathological hallmarks including deposits of the beta-amyloid (A beta) peptide. A beta is a 39- to 43-amino acid peptide derived from the proteolytic processing of the amyloid precursor protein (APP). While increasing evidence suggests that altered APP processing and A beta metabolism is a common feature of AD, the relationship between the levels of A beta and various APP products and the onset of AD remains unclear. We have undertaken a screen to characterize genetic factors that modify APP processing, A beta metabolism and A beta deposition in a genomic-based yeast artificial chromosome (YAC) transgenic mouse model of AD. A mutant human APP YAC transgene was transferred to three inbred mouse strains. Despite similar levels of holo-APP expression in the congenic strains, the levels of APP C-terminal fragments as well as brain and plasma A beta in young animals varied by genetic background. Furthermore, we demonstrate that age-dependent A beta deposition in the APP YAC transgenic model is dramatically altered depending on the congenic strain examined. These studies demonstrate that APP processing, A beta metabolism and A beta deposition are regulated by genetic background and that analysis of these phenotypes in mice should provide new insights into the factors that regulate AD pathogenesis. SN - 0964-6906 UR - https://www.unboundmedicine.com/medline/citation/14506131/Genetic_background_regulates_beta_amyloid_precursor_protein_processing_and_beta_amyloid_deposition_in_the_mouse_ L2 - https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/ddg322 DB - PRIME DP - Unbound Medicine ER -