Human Nasal Beta-amyloid 42 Reflects Cognition Decline in Alzheimer’s Disease

Abstract

Background: The key in Alzheimer’s disease (AD) therapy is a timely and accurate diagnosis for prompt drug intervention. However, due to the high cost and invasiveness of conventional biomarker analyses, including brain positron emission tomography (PET) imaging and cerebrospinal fluid (CSF)-based assays, easy accessibility to these screening tests is often hindered. There is, therefore, a great need to develop a more accessible biomarker screening test using less invasive and cost-effective peripheral body fluid biomarkers. Previous studies examined the non-quantitative expression of beta-amyloid (Aβ) in normal and AD patients' nasal discharge fluid. They identified higher expression of oligomeric Aβ in AD patients, showing a correlation with cognitive decline. However, the quantitative measurements of nasal Aβ42 levels, including the full AD continuum, remain unknown. Here, we assessed whether quantified human nasal Aβ42 levels could identify patients with AD and differentiate them from non-AD patients. Method: 161 subjects (cognitively normal (CN), n=32; preclinical, n=29; mild cognitive impairment (MCI), n=73; AD, n=27) underwent neuropsychological battery tests. Their nasal discharge samples were collected, and nasal Aβ42 levels were measured via enzyme-linked immunosorbent assay (ELISA). Result: We found that the second-highest quartile (Q3) group of nasal Aβ42 constituted the majority of patients with AD diagnosis (p=0.036). The Q3 group also outnumbered the other groups in the most cognitively impaired subjects in all three neuropsychological battery tests (p=0.033; p=0.0212; p=0.0147). Conclusion: Quantified nasal Aβ42 is strongly associated with cognition measurements. Nasal Aβ42 suggests the possibility for discriminating AD from non-AD.