Diffuse plaques contain C-terminal A β42 and not A β40: Evidence from cats and dogs

Abstract

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 Aβ 42 3 fragments (i.e., Aβ forms extending to residues 42 and/or 43) are thought to be predominant within diffuse plaques while both Aβ 42 3 and A β 40 (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 A β 1–17, A β 17–24, A β 1–28, A β 40, and A β 42. We report that plaques within the canine and feline brain are immunopositive for A β 42 but not A β 40. This is the first observation of nascent AD pathology in the aged feline brain. Canine plaques also contained epitopes within A β 1–17, A β 17–24, and Aβ 1–28 . In all species examined, vascular deposits were immunopositive for both A β 40 and A β 42. In the human brain, diffuse plaques were preferentially A β 42 immunopositive, while neuritic plaques and vascular deposits were both A β 40 and A β 42 immunopositive. However, not all neuritic plaques contain A β 40 epitopes.