Novel Biomarkers for Alzheimer's Disease: Plasma Neurofilament Light and Cerebrospinal Fluid

Abstract

Neurodegenerative disorders such as Alzheimer's disease (AD) represent an increasingly significant public health concern. As clinical diagnosis faces challenges, biomarkers are becoming increasingly important in research, trials, and patient assessments. While biomarkers like amyloid-β peptide, tau proteins, CSF levels (Aβ, tau, and p-tau), and neuroimaging techniques are commonly used in AD diagnosis, they are often limited and invasive in monitoring and diagnosis. For this reason, blood-based biomarkers are the optimal choice for detecting neurodegeneration in brain diseases due to their noninvasiveness, affordability, reliability, and consistency. This literature review focuses on plasma neurofilament light (NfL) and CSF NfL as blood-based biomarkers used in recent AD diagnosis. The findings revealed that the core CSF biomarkers of neurodegeneration (T-tau, P-tau, and Aβ42), CSF NFL, and plasma T-tau were strongly associated with Alzheimer's disease, and the core biomarkers were strongly associated with mild cognitive impairment due to Alzheimer's disease. Elevated levels of plasma and cerebrospinal fluid NfL were linked to decreased [18F]FDG uptake in corresponding brain areas. In participants with Aβ positivity (Aβ+), NfL correlated with reduced metabolism in regions susceptible to Alzheimer's disease. In addition, CSF NfL levels correlate with brain atrophy and predict cognitive changes, while plasma total tau does not. Plasma P-tau, especially in combination with Aβ42/Aβ40, is promising for symptomatic AD stages. Though not AD-exclusive, blood NfL holds promise for neurodegeneration detection and assessing treatment efficacy. Given the consistent levels of T-tau, P-tau, Aβ42, and NFL in CSF, their incorporation into both clinical practice and research is highly recommended.

Figure 1

A brief diagram showing existing biomarkers and emerging blood-based biomarkers used in AD diagnosis.