Comparison of CSF and plasma NfL and pNfH for Alzheimer’s disease diagnosis. A memory clinic study.

Abstract

Abstract Background Plasma neurofilament light chain (NfL) is a promising biomarker of axonal and neuronal damage in central nervous system disorders, displaying potential for the differential diagnosis of neurodegenerative diseases. The heavy chain of the neurofilaments, and specifically the phosphorylated form (pNfH), has demonstrated its value in amyotrophic lateral sclerosis diagnosis but has much less been explored in neurocognitive disorders. Our aim was to compare the positive and differential diagnosis performance of NfL, CSF and plasma pNfH in patients from daily clinical practice in Alzheimer’s disease (AD) and other dementias.Methods In a cross-sectional retrospective study, we compared NfL and pNfH levels in CSF and plasma for AD diagnosis in n = 188 patients from the Center of Cognitive Neurology, Lariboisiere Hospital, Paris, France including AD at the mild cognitive impairment (MCI) stage (AD-MCI, n = 36) and at the dementia stage (n = 64), as well as non-AD MCI (n = 38), non-AD dementia (n = 28) patients and neurological controls (NC) (n = 22). Plasma NfL, plasma and CSF pNfH levels were measured using the Simoa technique and CSF NfL using Elisa.Results NfL and pNfH, in plasma and CSF, were associated with age (rho = 0.259–0.451, P < 0.003). The correlation between CSF and plasma levels was stronger for NfL than pNfH (respectively, rho = 0.77 and rho = 0.52, respectively). Both CSF and plasma NfL and CSF pNfH were associated with CSF p-tau levels in AD patients, but not plasma pNfH. All neurofilament markers were increased in AD-MCI, AD dementia and non-AD dementia compared with NC. CSF NfL, CSF pNfH and plasma NfL showed high performance to discriminate AD at both MCI and dementia stage from control subjects (AUC = 0.82–0.91). Conversely, plasma pNfH displayed overall lower AUCs for discrimination between groups compared with CSF pNfH. Nfs markers showed moderate association with cognition. NfL displayed significant association with mediotemporal lobe atrophy and white matter lesions, in the whole cohort and in the AD subgroup.Conclusion CSF NfL and pNfH as well as plasma NfL displayed equivalent performance in both positive and differential AD diagnosis in a memory clinic setting. In contrast to motoneuron disorders, plasma pNfH did not demonstrate added value as compared with plasma NfL.