Human nasal beta-amyloid 42 has a diagnostic value in discriminating 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 have diagnostic performance and have the potential to be utilized as a biological risk factor in AD.

Method: 161 subjects (cognitively normal (CN), n=32; preclinical, n=29; mild cognitive impairment (MCI), n=73; AD, n=27) underwent neuropsychological battery tests, including Mini-Mental State Examination (MMSE), Clinical Dementia Rate (CDR), and Global Deterioration Scale (GDS), and amyloid-PET scans (18F-Flutemetamol). 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=0.008, p=0.037, p=0.023). Next we also found that subjects in the Q3 group exhibited most impaired cognitive function in all three neuropsychological battery tests with strong significance. When we examined the amyloid-PET SUVR values, subjects with PET positive showed the highest SUVR.

Conclusion: Quantified nasal Aβ42 is strongly associated with cognition measurements. Nasal Aβ42 suggests the possibility for discriminating AD from non-AD. © 2023 the Alzheimer's Association.