Plasma Neurofilament Light Predicts All-Cause Mortality Risk

Neurofilament light chain (NfL) is a cytoskeletal protein component exclusively expressed in neurons that is released into the extracellular fluids, including blood, during neuroaxonal damage. NfL is linked to mortality in neurological disorders, remaining unexplored in population studies.

NfL reflects sub-cortical large-caliber axonal degeneration. Plasma NfL levels correlate strongly with cerebrospinal fluid (CSF) NfL levels, adding to its clinical utility in differential diagnoses for dementias and other neurodegenerative diseases. Therefore, plasma NfL measurements are advantageous given the invasiveness of CSF assessments and feasibility for long-term monitoring.

Scientists at the National Institute on Aging (Baltimore, MD, USA) collected longitudinal data from 694 participants in the Healthy Aging in Neighborhoods of Diversity Across the Life Span study (HANDLS, mean age first visit [v1]: 47.8 years, 42% male, 55.8% African American). Fasting blood samples were collected between 9:30 am and 11:30 am into EDTA blood collection tubes.

Plasma NfL was measured prospectively at three visits. Plasma NfL levels were quantified using the Simoa NF-light Advantage Kit on a Simoa HD-X analyzer by Quanterix (Billerica, MA, USA). Total cholesterol (mg/dL), HDL cholesterol (mg/dL), high-sensitivity C-reactive protein (hsCRP) (mg/dL), albumin (g/dL), and glycosylated hemoglobin (HbA1c) (%) were quantified by contract laboratories (Quest Diagnostics, Chantilly, VA, USA). In this study, the δNfL is the annualized rate of change between NfLv1, NfLv2, and NfLv3, on average, when these measurements were Loge-transformed.

The team reported that most notably, men had significantly higher plasma NfL (Loge-transformed) compared to women at both visits 1 and 3. These differences remained comparable after further adjustment for age, race, and poverty status. Moreover, men were more likely than women to be pre-diabetic, with the reverse being observed in the case of diabetes. Self-reported history of cardiovascular disease (CVD) was more prevalent in women (15.9% versus 8.7%). Several continuous components of AL were higher among women, namely hsCRP, total cholesterol, and HDL cholesterol, while the reverse was observed for albumin and diastolic blood pressure (DBP). Similar patterns were observed for binary AL components. Notably, NfLv1 was shown to be a better prognostic indicator at normal hsCRP values among women, while HbA1c and δNfL interacted synergistically to determine mortality risk, overall.

The authors concluded that plasma NfL levels measured both at baseline and over time can predict all-cause mortality in women. The study was published on June 13, 2022 in the journal BMC Medicine.

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