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Amyloid production and deposition in mutant amyloid precursor protein and presenilin-1 yeast artificial chromosome transgenic mice

Abstract

Dosage imbalance for chromosome 21 in Down syndrome and mutations in the amyloid precursor protein (APP) and presenilin-1 (PS-1 ) genes in early-onset familial Alzheimer's disease (FAD) result in elevated production and deposition of amyloid-β (Aβ) peptides1, particularly the 42 amino acid form, Aβ1–42. One difficulty in studying the generation and deposition of Aβ, neuritic abnormalities, synaptic dysfunction, neuronal cell death and dementia that occurs in Alzheimer's disease (AD) is the paucity of small animal models. To examine effects of the FAD mutations in vivo, we transferred yeast artificial chromosomes (YACs) containing the entire genomic copy of human APP and/or PS-1 genes harboring FAD mutations into transgenic mice2,3. We now document that a mutant APP YAC transgenic mouse develops Aβ deposits and that this deposition is accelerated when the animals are mated to homozygosity and/or to mutant PS-1 YAC transgenic mice.

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Figure 1: Generation and characterization of PS-1 YAC transgenic mice.
Figure 2: Amyloid deposits in APP and APP/PS-1 YAC transgenics.

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Acknowledgements

This work was supported by National Institutes of Health Grants AG14451 and AG08012 (B.T.L.), T32 GM08613 (E.J.H.), and AG14248 (S.S.S.), the American Health Assistance Foundation (S.S.S.) and the Bristol-Meyers Squibb Pharmaceutical Research Institute (S.L.W.).

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Correspondence to Bruce A. Lamb.

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Lamb, B., Bardel, K., Kulnane, L. et al. Amyloid production and deposition in mutant amyloid precursor protein and presenilin-1 yeast artificial chromosome transgenic mice. Nat Neurosci 2, 695–697 (1999). https://doi.org/10.1038/11154

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