Is NfL the New 'N' in A/T/N Classification of Alzheimer’s?

Neurofilament light (NfL) measured in cerebrospinal fluid predicts mild cognitive impairment better than other CSF indicators of neurodegeneration, according to the November 12 JAMA Neurology. Scientists led by Michelle Mielke, Mayo Clinic, Rochester, Minnesota, report that in a large, community-based sample, people with high CSF NfL were three times more likely to develop MCI during follow-up than those with low NfL. Alzforum first reported these findings at this year’s AAIC (Aug 2018 conference news). 

  • People with high CSF NfL are likely to develop MCI.
  • No other biomarkers of neurodegeneration predicted MCI in this sample.
  • CSF NfL may be a good biomarker for the “N” in A/T/N.

First author Silke Kern, University of Gothenburg, Mölndal, Sweden, and colleagues used longitudinal data collected from 648 non-demented people, average age 72, in the prospective Mayo Clinic Study of Aging. Researchers measured cognition, and CSF NfL, neurogranin, total tau, phosphorylated tau, and Aβ42 at baseline. The present analysis includes data from participants who had been observed for an average of 3.8 years, sitting for neuropsychological tests every 15 months. During that time, 94 people developed MCI and four dementia, diagnosed according to Petersen (Petersen et al., 2004) and DSM-IV criteria, respectively.

People in the highest tertile of measured CSF NfL values had a 3.1-fold higher risk of developing MCI/dementia than people in the bottom tertile. Neither the tau nor neurogranin measures predicted this early cognitive decline. As in previous studies, low Aβ42 associated with risk for MCI, though that did not change NfL’s ability to predict risk, suggesting the two affect disease independently.

The results further establish CSF NfL as a biomarker for early neurodegeneration. It is not specific for Alzheimer’s but, the authors write, may be the preferred “N” marker for the A/T/N classification proposed in the current revision of the NIA-AA criteria for a biological diagnosis of AD (Jack et al., 2018). 

The scientists are currently testing the predictive value of plasma NfL in this population.—Gwyneth Dickey Zakaib

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References

News Citations

  1. Blood Test for Neurofilament Light Chain Kicks Up Biomarker Research

Paper Citations

  1. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004 Sep;256(3):183-94. PubMed.
  2. Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R, Contributors. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018 Apr;14(4):535-562. PubMed.

Further Reading

Primary Papers

  1. Kern S, Syrjanen JA, Blennow K, Zetterberg H, Skoog I, Waern M, Hagen CE, van Harten AC, Knopman DS, Jack CR Jr, Petersen RC, Mielke MM. Association of Cerebrospinal Fluid Neurofilament Light Protein With Risk of Mild Cognitive Impairment Among Individuals Without Cognitive Impairment. JAMA Neurol. 2018 Nov 12; PubMed.

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