Recent reports have suggested that β-amyloid (Aβ) species of variable length C-termini are differentially deposited within early and late-stage plaques and the cerebrovasculature. Specifically, longer C-terminal length A β _{42 3} fragments (i.e., Aβ forms extending to residues 42 and/or 43) are thought to be predominant within diffuse plaques while both A β _{42 3} and Aβ₄₀ (Aβ forms terminating at residue 40) are present within a subset of neuritic plaques and cerebrovascular deposits. We sought to clarify the issue of differential Aβ deposition using aged canines, a partial animal model of Alzheimer's disease that exhibits extensive diffuse plaques and frequent vascular amyloid, but does not contain neuritic plaques or neurofibrillary tangles. We examined the brains of 20 aged canines, 3 aged felines, and 17 humans for the presence of Aβ immunoreactive plaques, using antibodies to Aβ_1–17, Aβ_17–24, Aβ_1–28, Aβ₄₀, and Aβ₄₂. We report that plaques within the canine and feline brain are immunopositive for Aβ₄₂ but not Aβ₄₀. This is the first observation of nascent AD pathology in the aged feline brain. Canine plaques also contained epitopes within Aβ_1–17, Aβ_17–24, and Aβ_1–28. In all species examined, vascular deposits were immunopositive for both Aβ₄₀ and Aβ₄₂. In the human brain, diffuse plaques were preferentially Aβ₄₂ immunopositive, while neuritic plaques and vascular deposits were both Aβ₄₀ and Aβ₄₂ immunopositive. However, not all neuritic plaques contain Aβ₄₀ epitopes.