CSF neurofilament light a ‘preferred’ biomarker for MCI progression
medwireNews: Elevated cerebrospinal fluid (CSF) neurofilament light levels (NfL) are associated with an increased risk of mild cognitive impairment (MCI), indicate findings from a population-based study.
Among 648 individuals without cognitive impairment, those in the highest quartile for CSF NfL had a significant 2.9-fold increased risk for developing MCI, compared with those in the lowest quartile, after taking into account age, sex, level of education and comorbidities. The risk increased further still to 3.1-fold after additional adjustment for apolipoprotein E (APOE) genotype.
There was no significant increased risk for individuals in CSF NfL quartiles 2 and 3, however. And Michelle Mielke (Mayo Clinic, Rochester, Minnesota, USA) and colleagues report that neither CSF total tau (T-tau), phosphorylated tau (P-tau) nor neurogranin (Ng) levels were associated with a heightened risk of progressing to MCI.
Noting the potential for CSF NfL and T-tau to “contribute divergent information regarding neurodegeneration”, the researchers looked at whether combining the two measures heightened the risk of MCI, but they found that participants with only CSF NfL in the highest quartile had a similar level of risk to those with both CSF NfL and T-tau in the highest quartile, at 2.2-fold and 2.3-fold, respectively.
“These findings suggest that CSF NfL is a stronger predictor of cognitive deterioration than T-tau in a population-based sample of [participants without cognitive impairment]”, say the researchers, adding that this supports the thinking that they have unique neurodegenerative roles.
“Cerebrospinal fluid NfL is a measure of axonal injury, whereas CSF T-tau probably reflects the temporal course and severity of neuronal injury at a given point”, they write in JAMA Neurology.
The study participants were aged a median of 72.3 years and 56.5% were men. In all, 14.8% progressed to MCI over a median 3.8 years of follow-up. Individuals who progressed to MCI were more frequently carriers of an APOE ε4 allele, at a rate of 36.5% versus 24.9% among those who did not progress.
Continuous measures of CNS NfL showed that each log unit increase in levels was associated with a 1.32-fold increased risk of MCI. There was also a significant association between each log unit increase in CSF Aβ42 and a decreased risk of MCI. But when this factor was assessed across quartiles, there was only a significantly reduced MCI risk for individuals in quartile 3 once APOE status had been taken into account.
The association between CNS NfL and MCI risk was also independent of CSF Aβ42 levels, which the team says indicates “CNS NfL is a risk factor for cognitive impairment for those on the [Alzheimer’s disease] pathway (with low CSF Aβ42 levels) and for those who are not”, reflecting a role as a “non-specific marker of neurodegeneration.”
Mielke and colleagues conclude that their data suggest that NfL could be “the preferred” CSF biomarker of neurodegeneration and neuronal injury in the 2018 National Institute on Aging-Alzheimer Association criteria for the β-amyloid biomarker/tau biomarker/neurodegeneration or neuronal injury biomarker classification.
By Lucy Piper
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