Potential biomarkers for Alzheimer's disease (AD) include amyloid β_1-42 (Aβ_1-42), t-Tau, p-Tau₁₈₁, neurofilament light chain (NFL), and neuroimaging biomarkers. Their combined use is useful for diagnosing and monitoring the progress of AD. Therefore, further development of a combination of these biomarkers is essential. We investigated whether plasma NFL/Aβ_1-42 can serve as a plasma-based primary screening biomarker reflecting brain neurodegeneration and amyloid pathology in AD for monitoring disease progression and early diagnosis. We measured the NFL and Aβ_1-42 concentrations in the CSF and plasma samples and performed correlation analysis to evaluate the utility of these biomarkers in the early diagnosis and monitoring of AD spectrum disease progression. Pearson's correlation analysis was used to analyse the associations between the fluid biomarkers and neuroimaging data. The study included 136 participants, classified into five groups: 28 cognitively normal individuals, 23 patients with preclinical AD, 22 amyloid-negative patients with amnestic mild cognitive impairment, 32 patients with prodromal AD, and 31 patients with AD dementia. With disease progression, the NFL concentrations increased and Aβ_1-42 concentrations decreased. The plasma and CSF NFL/Aβ_1-42 were strongly correlated (r = 0.558). Plasma NFL/Aβ_1-42 was strongly correlated with hippocampal volume/intracranial volume (r = 0.409). In early AD, plasma NFL/Aβ_1-42 was associated with higher diagnostic accuracy than the individual biomarkers. Moreover, in preclinical AD, plasma NFL/Aβ_1-42 changed more rapidly than the CSF t-Tau or p-Tau₁₈₁ concentrations. Our findings highlight the utility of plasma NFL/Aβ_1-42 as a non-invasive plasma-based biomarker for early diagnosis and monitoring of AD spectrum disease progression.

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