β-Amyloid Peptide and Amyloid Precursor Proteins in Olfactory Mucosa of Patients with Alzheimer's Disease, Parkinson's Disease, and down Syndrome

Abstract

Dystrophic neurites are present in olfactory epithelium (OE) of patients with Alzheimer's disease (AD), Parkinson's disease (PD), and Down syndrome (DS) and occasionally in normal individuals. Cultured olfactory neuroblasts from AD patients generate carboxy terminal amyloid precursor protein (APP) fragments that contain β-amyloid (Aβ), but it is not known if deposits of Aβ and/or APP fragments occur in the OE of individuals with or without AD, PD, or DS. To determine if Aβ accumulates in the OE in situ, we probed postmortem samples of olfactory mucosa from patients with AD, PD and AD (PD/AD), and DS and AD (DS/AD), as well as from controls, using polyclonal and monoclonal antibodies to Aβ and flanking sequences in APPs. Samples of OE also were examined by thioflavin-S and electron microscopy. Labeling of Aβ was observed in 10 of 12 AD cases, 2 of 3 PD/AD cases, 3 of 4 DS/AD cases, 3 of 10 adult controls, and 4 of 6 fetal cases. The Aβ staining was seen in the basal third of the OE, in axons projecting through the lamina propria, and in metaplastic respiratory epithelium within the OE. Antibodies to other APP domains stained the OE of patients and controls. Thioflavin-S staining was present in the basal third of the OE of 8 of 9 AD patients and several PD/AD and DS/AD patients, but only in rare cells of 3 controls. Electron microscopy did not reveal amyloid fibrils in the OE. These data suggest that deposition of Aβ occurs in a variety of circumstances and is not restricted to patients with AD, PD, or DS.