Blood biomarker shows “great promise” predicting progression to Alzheimer’s in at-risk population

Researchers in the field of neuroscience at Wayne State University have recently published a review article affirming the utility of neurofilament light (NfL) levels in the blood as a predictor of the likelihood and pace of neurodegeneration progression in Alzheimer’s disease.

Blood-based NfL serves as a minimally invasive and readily accessible biomarker, rendering it valuable in clinical assessments. The review, authored by Youjin Jung, a doctoral student in the Behavioral and Cognitive Neuroscience program and a trainee at WSU’s Institute of Gerontology, and Jessica Damoiseaux, Ph.D., an associate professor in the Institute of Gerontology and the Department of Psychology, comprehensively analyzed existing literature to explore the relationship between serum or plasma NfL levels and structural/functional brain imaging metrics of neurodegeneration obtained from MRI or PET imaging.

While NfL levels also rise with typical aging as a non-specific indicator of neuronal damage, the levels and rate of increase observed in Alzheimer’s dementia are notably higher. Jung and Damoiseaux’s findings indicate that elevated blood NfL levels are indicative of the extent of atrophy in multiple overlapping brain regions, particularly the medial temporal lobe. Furthermore, higher serum NfL levels correlate with more pronounced brain glucose hypometabolism and diminished white matter integrity in individuals within the Alzheimer’s disease spectrum.

Damoiseaux highlighted the potential of blood NfL as a monitoring biomarker, stating, “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. It 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 consistently revealed significant associations between blood NfL levels and atrophy in brain regions susceptible to Alzheimer’s disease pathology. Damoiseaux noted, “We found that an increase in blood NfL may precede Alzheimer’s disease-related changes in cortical atrophy and may be elevated in the preclinical stages of Alzheimer’s disease.”

The comprehensive review of cross-sectional and longitudinal literature underscores the consistent predictive value of blood NfL levels regarding the extent of atrophy and glucose metabolism abnormalities in brain regions commonly affected by Alzheimer’s pathology. The work by Jung and Damoiseaux emphasizes that blood NfL serves as a valuable prognostic marker for forecasting neurodegeneration progression and assessing the risk of abnormal changes in brain structure and function in cognitively unimpaired individuals with a heightened Alzheimer’s disease risk, such as those with the APOE ε4 allele.

Jung cautioned, however, that there are still gaps in knowledge to be addressed concerning the appropriate use of blood NfL as a biomarker. “We need more studies on how blood NfL is related to different aspects of neuronal damage,” she remarked, “and the field should seek to learn more about potential factors that may affect the NfL concentration in the blood.”

The review article, titled “The Potential of Blood Neurofilament Light as a Marker of Neurodegeneration in Alzheimer’s disease,” was published in the journal Brain on August 4, 2023, and can be accessed via doi.org/10.1093/brain/awad267.

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