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.
Highlights
Neurodegenerative dementias, Alzheimer’s disease (AD), are an accelerating health and economic issue that affects more than 46.8 million patients worldwide, and it is estimated that, by 2035, this number will likely double without modifiable or preventive treatment (Martin Prince et al, 2015)
Patients with dementia with Lewy bodies (DLB) fulfilled the criteria from the fourth report of the DLB consortium (McKeith et al, 2017), patients with NPH were diagnosed according to international guideline criteria for idiopathic normal pressure hydrocephalus (Relktin et al, 2005), while the diagnosis alcohol-induced dementia was established according to the International Classification of Diseases (ICD)-10 criteria (ICD10, 2020)
A total of 152 patients and 17 healthy controls (HCs) with saliva samples were included in the study, and 135 of these had a matching plasma sample
Summary
Neurodegenerative dementias, Alzheimer’s disease (AD), are an accelerating health and economic issue that affects more than 46.8 million patients worldwide, and it is estimated that, by 2035, this number will likely double without modifiable or preventive treatment (Martin Prince et al, 2015). The diagnosis of dementia relies primarily on neurological and psychological assessment, imaging modalities, and analyses of the cerebrospinal fluid (CSF), especially tau, phosphorylated tau (p-tau), and beta amyloid 1–42 (Aβ42), some of which are specific to AD pathology Some of these methods require special training to perform, are regarded as invasive, and may in a percentage of cases lead to adverse reactions (Costerus et al, 2018). Considerable economic resources are often spent, and some imaging methods cause radiation and lack molecular specificity (Lin, 2010) For these reasons, it is essential to develop new non-invasive and inexpensive methods that can differentiate between neurodegenerative and non-neurodegenerative diseases in representative clinical settings. While blood biomarkers are considerably less complexed than CSF and molecular imaging, venipuncture is still required to extract the sample that may still limit some populations
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