Neurofilament Light Chain Identified as Cross-Species Biomarker for Aging and Mortality Risk

Researchers at the German Center for Neurodegenerative Diseases (DZNE) and the Hertie Institute for Clinical Brain Research (HIH) at the University of Tübingen have identified the protein neurofilament light chain (NfL) as a biomarker detectable in the blood of numerous animal species, with levels increasing with age in mice, cats, dogs, and horses. The findings were reported in the scientific journal PLOS Biology.

The protein NfL is an indicator of nerve damage. It is released when neurons undergo change or degenerate, either as a result of disease or with normal aging. NfL can then enter the bloodstream and be detected using sensitive analysis techniques. In neurodegenerative diseases such as Alzheimer's and ALS, NfL is found at elevated levels in the blood. However, the concentration also rises in healthy people with age.

Neurofilament light chain serves as a critical structural component of neurons, forming part of the cytoskeletal network within axons. Under conditions of neuronal stress, damage, or degeneration—common in various neurological disorders and aging—NfL is released into the extracellular space and eventually enters the bloodstream. The detection of NfL in plasma or serum has emerged as a sensitive technique for evaluating neuronal integrity and neurodegeneration.

In longitudinal observations of 44 elderly mice, blood NfL levels were monitored regularly over 4 months. Those with slowly rising NfL levels lived comparatively longer, while faster increases were linked to shorter lifespans. Studies have revealed that the concentration of NfL in the blood of elderly people is associated with an increased risk of death, suggesting a link between neurological aging and mortality.

In addition to cats, dogs, horses, and mice, a further 53 animal species were examined on a sampling basis. This included rabbits, lions, monkeys, elephants, reptiles, and birds. This was done in collaboration with the zoo in Stuttgart, Germany, the Vetsuisse Faculty at the University of Zurich, and a veterinary diagnostics laboratory. The NfL protein was detected in the blood of all mammals, but only in some reptiles and birds, such as a crocodile and a parrot.

A possible explanation for limited detection in non-mammalian species is that the NfL protein sequence in these animals differs slightly from its human counterpart, and therefore could not be detected by the assay used in the present study. Differences in the protein's amino acid sequence across taxa may reduce assay sensitivity, necessitating customized detection methods in future research.

The technical backbone of this research hinges on the use of highly sensitive immunoassays capable of quantifying minute concentrations of NfL in blood samples. These assays detect epitopes on the protein's structure, which, given evolutionary variations, may sometimes limit detection in certain species.

The research suggests this biomarker could help to assess the biological age of animals and estimate their life expectancy. Analysis methods from dementia research are promising for veterinary medicine, when it comes to assessing the biological age, neurological health, and life expectancy of animals.