Scientists at the German Center for Neurodegenerative Diseases (DZNE), the Hertie Institute for Clinical Brain Research (HIH) and the University Hospital Tübingen now show that a protein found in the blood can be used to precisely monitor disease progression long before first clinical signs appear.
When brain cells die, their remains can be detected in the blood. However, most proteins degrade too rapidly.
Neurofilament light chain (NfL) is resistant to breaking down in the blood. Scientists have shown that neurofilament accumulates in the blood long before the onset of clinical symptoms and it very sensitively reflects the course of Alzheimer’s disease and enables predictions on future developments.
Omens of dementia
Jucker and his colleagues monitored the development of neurofilament concentration in these individuals from year to year. Up to 16 years before the calculated onset of dementia symptoms, there were noticeable changes in the blood. “It is not the absolute neurofilament concentration, but its temporal evolution, which is meaningful and allows predictions about the future progression of the disease,” says Jucker. In fact, in further investigations, the scientists showed that changes in neurofilament concentration reflect neuronal degradation very accurately and allow predictions on how brain damage will develop. “We were able to predict loss of brain mass and cognitive changes that actually occurred two years later,” says Jucker.
Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer’s disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini–Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer’s disease, which supports its potential utility as a clinically useful biomarker.
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