Blood biomarker shows promise in predicting Alzheimer’s disease progression
A recent review article confirms the utility of blood-based neurofilament light (NfL) as a clinical biomarker in Alzheimer’s disease.
As populations age and the number of people living with Alzheimer’s disease increases, tools that can help predict the likelihood and rate of progression of neurodegeneration are vital. Researchers at Wayne State University (MI, USA) reviewed existing literature to see if NfL could be an effective biomarker for this.
NfL is a neuronal cytoplasmic protein highly expressed in large, myelinated axons, which has proven useful in identifying axonal damage and neurodegeneration. NfL is often measured as a non-specific biomarker for several neurodegenerative conditions, including multiple sclerosis and amyotrophic lateral sclerosis. Levels of NfL found in the blood serve as a minimally invasive and easily accessible biomarker, rendering it useful to clinical investigation. The researchers conducted a comprehensive literature review exploring the association between serum or plasma levels of NfL and brain imaging measures of neurodegeneration, obtained from MRI or PET imaging.
Although an increase in blood-based NfL has been associated with typical aging, levels are notably higher in Alzheimer’s disease. The findings presented in the review suggest that high levels of NfL reflect the extent of atrophy in several overlapping brain regions, particularly the medial temporal lobe. High serum NfL also correlates with a decline in white matter integrity and worsened brain glucose hypometabolism in individuals with Alzheimer’s disease.
“The cross-sectional literature indicates that blood NfL shows great promise as a monitoring biomarker to indicate the severity of neurodegeneration in Alzheimer’s disease”, commented corresponding author Jessica Damoiseaux. This could be “especially useful in persons who show Alzheimer’s pathology but are at present cognitively unimpaired, or in people who are highly likely to develop Alzheimer’s disease due to having the APOE ε4 allele or higher Aβ load.”
Longitudinal studies also repeatedly showed a significant relationship between NfL and atrophy in brain regions associated with Alzheimer’s disease pathology. The researchers concluded that blood NfL is elevated in the early stages of disease and may precede decreases in cortical function.
The review of cross-sectional and longitudinal literature highlights the utility of blood-based NfL levels in predicting the severity of brain atrophy and glucose metabolism in brain areas commonly impacted by Alzheimer’s pathology. The review indicates that blood NfL may serve as a useful marker to predict the risk and progression of neurodegeneration.
Despite the promising data, gaps in knowledge remain regarding the role of NfL as a biomarker. First author Youjin Jung suggests that “we need more studies on how blood NfL is related to different aspects of neuronal damage, and the field should seek to learn more about potential factors that may affect the NfL concentration in the blood.” Other limitations include difficulty in measuring peak NfL concentrations, and accounting for the presence of comorbidities that could also affect NfL levels.
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