Establishing an Alzheimer's disease biomarker based on beta-amyloid analysis using postmortem samples, olfactory bulb and nasal mucosawith scrapings

Background: Amyloid imaging (AI) is in clinical application, but there are still no prospects despite the urgent need for establishing a simple test athome diagnostic test. We identified β-amyloid (Aβ) in the nasal cavity in AD animal models. We have also observed the Aβ correlation in the brain. If it could also be verified in Alzheimer disease (AD) patients, a rapid biomarker test for AD could potentially be developed. In this study, we have attempted to analyze Aβ in the olfactory bulb, the nasal mucosa and scraping fluid from the mucosa using human autopsy samples. Methods: For use of human brain specimens, we obtained nasal tissue and scraping samples from the Fukushimura Brain Bank. After autopsy, tissues were fixed in formalin and them, embedded in paraffin for staining with anti-Aβ and antiphosphorylated tau antibodies. The snap frozen samples were analyzed using ELISA, Western blotting and mass spectrometry (nasal mucosa and scraping fluid) semi-quantitatively. Results: The presence of Aβ was confirmed in the olfactory bulb, nasal mucosa and nasal secretions of AD patients. Conclusions: We detected Aβ in the olfactory bulb, nasal mucosa and mucosal scrapings. Considering the possible clinical application, the sampling method and detection limit must be improved. Together with neuropathological confirmatory investigations, a multi-center clinical trial employing a combination of AI is necessary.