Saliva Neurofilament Light Chain Is Not a Diagnostic Biomarker for Neurodegeneration in a Mixed Memory Clinic Population

Abstract

Neurodegeneration and axonal injury result in an increasing release of neurofilament light chain (NfL) into bodily fluids, including cerebrospinal fluid (CSF) and blood. Numerous studies have shown that NfL levels in CSF and blood are increased in neurodegenerative disorders and monitor neurodegeneration. Saliva is an easily accessible biofluid that could be utilized as a biofluid measurement of Alzheimer’s disease (AD) biomarkers. In this study, for the first time, salivary NfL was measured and compared to plasma NfL in a consecutive cohort of patients referred to cognitive assessments. In two mixed memory clinic cohorts, saliva samples were taken from 152 patients, AD (n = 49), mild cognitive impairment (MCI) (n = 47), non-AD (n = 56), and also 17 healthy controls. In addition, 135 also had a matching plasma sample. All saliva and plasma samples were analyzed for NfL, and the association between saliva and plasma NfL and CSF levels of total tau (t-tau), phosphorylated tau (p-tau), and beta amyloid 1–42 (Aβ42) were investigated. In total, 162/169 had quantifiable levels of salivary NfL by single molecule array (Simoa). No statistically significant differences were found in salivary NfL concentration across the diagnostic groups, but as expected, significant increases were found for plasma NfL in dementia cases (P < 0.0001). There was no association between saliva and plasma NfL levels. Furthermore, saliva NfL did not correlate with CSF Aβ42, p-tau, or tau concentrations. In conclusion, NfL is detectable in saliva but does not reflect neurodegeneration in the brain.

Salivary Metabolomics in the Diagnosis and Monitoring of Neurodegenerative Dementia

“…In plasma and CSF, NfL has been shown to be a promising biomarker for neurodegeneration. However, a similar trend has not been found using saliva samples [ 18 ].…”

The Added Value of Cerebrospinal Fluid Neurofilament Light Chain to Existing Diagnostic Methods and Biomarkers in a Mixed Memory Clinic Cohort of Consecutive Patients

“…Dementia diagnostics and biomarkers are highly developing fields and represents fruitful domains for new biomarkers, new sources to sample biomarkers [23,24], new technologies and the complex process of the clinical evaluation of a patient with a suspected dementia disorder. Better exploitation of already validated biomarkers is important for optimizing the diagnostic procedure, making it cost-effective and lessen the need for additional clinical evaluation.…”

Salivary inflammatory biomarkers are predictive of mild cognitive impairment and Alzheimer’s disease in a feasibility study

“…Only a few studies report total protein in saliva from individuals with MCI or AD. Three recent studies show a trend of increasing total protein in saliva from individuals diagnosed with MCI or AD ( Galindez et al, 2021 ; Gleerup et al, 2021a , b ). Higher levels of salivary protein have also been reported in saliva from individuals with Parkinson’s disease (PD) ( Devic et al, 2011 ; Al-Nimer et al, 2014 ; Kang et al, 2014 ; Fedorova et al, 2015 ; Masters et al, 2015 ; Galindez et al, 2021 ) and have been attributed to reduced saliva flow ( Fedorova et al, 2015 ) and PD related salivary gland dysfunction ( Masters et al, 2015 ).…”

“…Interestingly, levels of the amyloid-β (1–42) peptide have been shown to increase in AD saliva ( Bermejo-Pareja et al, 2010 ; Kim et al, 2014 ; Lee et al, 2017 ; Sabbagh et al, 2018 ; Katsipis et al, 2021 ), in contrast to the pattern of reduced levels observed in AD blood ( Nakamura et al, 2018 ). Other promising AD biomarkers detected in saliva include glial fibrillary acidic protein ( Katsipis et al, 2021 ), lactoferrin ( Carro et al, 2017 ; González-Sánchez et al, 2020 ; Gleerup et al, 2021a ; Reseco et al, 2021 ) and neuronal damage marker, neurofilament light chain ( Gleerup et al, 2021b ; Monroe et al, 2022 ).…”