Nasal Aβ42 mirrors brain amyloid dynamics and cognitive decline across the Alzheimer’s disease continuum

Abstract

Early, non-invasive assessment of Alzheimer’s disease (AD) progression remains a key challenge. This study evaluated whether nasal amyloid-β42 (Aβ42) levels reflect brain amyloid dynamics and cognitive decline. Nasal discharge from 161 individuals, ranging from cognitively unimpaired to AD dementia, was analyzed using ELISA, alongside neuropsychological assessments and amyloid PET imaging. Moderate nasal Aβ42 levels (9.53–11.10 pg/mL) were positively associated with PET amyloid burden and cognitive decline, identifying a critical transitional disease stage. Conversely, the highest Aβ42 levels showed weaker correlations, suggesting a non-linear progression. The pattern of nasal Aβ42 mirrored brain amyloid accumulation, which peaks and stabilizes in later disease stages. These findings highlight nasal Aβ42 as a promising, scalable biomarker for tracking AD pathology and offer the first evidence linking it with brain amyloid PET. This supports its potential use in both clinical and longitudinal research settings.