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) peptides 1, 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 mice 2, 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.