Tau Proteins Are Abnormally Expressed in Olfactory Epithelium of Alzheimer Patients and Developmentally Regulated in Human Fetal Spinal Cord

Abstract

In pathological conditions, the microtubule-associated tau proteins may accumulate in neuronal perikarya or be expressed de novo in certain populations of neurons. For example, olfactory epithelium (OE) neurons in Alzheimer's disease (AD) patients express tau in their axons when these axons become dystrophic. In this study, we examined human postmortem olfactory tissue with a panel of tau antibodies that bind to epitopes located in subdomains spanning nearly the entire length of all six known isoforms of human CNS tau. In addition, the developing human spinal cord was probed with a similar panel of tau antibodies to determine whether or not fetal tau epitopes were reexpressed in the dystrophic OE neurites of AD patients. Electron microscopy was performed to examine the ultrastructure of the filaments present in these dystrophic OE neurites. We show here that all the tau epitopes examined are expressed in dystrophic OE neurites of AD patients, but that certain tau epitopes are preferentially expressed in the dystrophic neurites of AD. We also demonstrate that many of the epitopes present in the dystrophic neurites of AD are expressed early in the developing spinal cord and are later extinguished, including adult tau epitopes present in the brain. Finally, our EM studies reveal the presence within dystrophic OE neurites of ∼10 to 15-nm-diameter filaments. These results suggest that the entire extent of multiple tau molecules is present in dystrophic OE neurites, with certain modifications of tau occurring preferentially in the dystrophic neurites of AD patients.