Characteristic changes that appear in the biopsied olfactory mucosa of patients with Alzheimer's disease (AD) were examined with immunohistochemical staining. Specimens were obtained from patients with clinical diagnoses of AD. Patients with vascular dementia and age-matched patients without dementia were used for controls. In most AD cases, neurofibrillary tangle-like abnormal tau protein (Tau) immunoreactivity was seen in the dendrites and perikarya of the olfactory receptor cells and in the nerve bundles. A senile plaque-like extracellular mass was found in the olfactory epithelium, and it reacted strongly to an anti-Tau antiserum and weakly to an anti-amyloid-beta protein antiserum. Ubiquitin (Ubq) immunoreactivity was also observed in the dendrites. Tau immunoreactivity of the perikarya and extracellular mass, and Ubq immunoreactivity were especially characteristic of the olfactory mucosa of AD patients. From these results, it is clear that the same pathologic changes in the brain are also present in the olfactory mucosa of patients with AD. Not only disruption of the central olfactory pathway, but also an olfactory disturbance of AD patients is caused by peripheral changes. Furthermore, an olfactory mucosal biopsy could be a useful method for a definitive diagnosis of AD.

Characteristic changes appearing in the biopsied olfactory mucosa of Alzheimer's disease (AD) patients were investigated using immunohistochemical staining. Specimens were obtained from 6

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