Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings

Abstract

Introduction: Many patients with cognitive and neuropsychiatric symptoms face diagnostic delay and misdiagnosis. We investigated whether cerebrospinal fluid (CSF) neurofilament light (NfL) and total-tau (t-tau) could assist in the clinical scenario of differentiating neurodegenerative (ND) from psychiatric disorders (PSY), and rapidly progressive disorders.Methods: Biomarkers were examined in patients from specialist services (ND and PSY) and a national Creutzfeldt-Jakob registry (Creutzfeldt-Jakob disease [CJD] and rapidly progressive dementias/atypically rapid variants of common ND, RapidND).

Plasma neurofilament light chain as a biomarker of Alzheimer’s disease in Subjective Cognitive Decline and Mild Cognitive Impairment

“…Indeed, despite MCI A− patients do not belong to AD continuum, they represent a defined pathological entity driven by both degenerative and non-degenerative (including cerebrovascular, infective, metabolic, or psychiatric) conditions [ 45 ]. In particular, a study by Eratne et al demonstrated the diagnostic utility of CSF NfL in differentiating neurodegenerative diseases from psychiatric disorders, with high accuracy [ 46 ]. Future studies may further investigate this point to assess the utility of NfLs in distinguishing psychiatric and neurodegenerative conditions among MCI not-due to AD.…”

microRNA-based predictor for diagnosis of frontotemporal dementia

“…Brain imaging and several biofluid proteins have been proposed as biomarkers for both ALS and FTD (Al Shweiki et al , 2019; Ashton et al , 2021; Bellini et al , 2022; Benussi et al , 2019; Bian et al , 2008; Borroni et al , 2015; Bourbouli et al , 2017; Bright et al , 2019; Chouliaras et al , 2022; Das et al , 2022; Delaby et al , 2020; Eratne et al , 2022; Feneberg et al , 2018; Forgrave et al , 2019; Goncalves et al , 2017; Gonzalez-Garza et al , 2018; Hansson et al , 2019; Hu et al , 2013; Jiskoot et al , 2019; Katisko et al , 2021; Katisko et al , 2020; Krishnan et al , 2022; McCarthy et al , 2018; Meeter et al , 2017; Meeter et al , 2018; Niikado et al , 2019; Oeckl et al , 2022; Prado et al , 2018; Rossi et al , 2018; Sheikh-Bahaei et al , 2017; Silva-Spinola et al , 2022; Teunissen et al , 2016; Thijssen et al , 2022; Turner et al , 2009; van der Ende et al , 2020; Verde et al , 2021; Wilson et al , 2022; Xu et al , 2016). Among the proteins, noticeable are neurofilament light chain (NfL), TDP-43 and, phospho-tau, amyloid beta and glial fibrillary acidic protein (GFAP).…”

Cerebrospinal fluid Alzheimer disease biomarkers for assessing cognitive and neuropsychiatric symptoms: Expanding the ‘toolkit’ in the psychiatrist’s diagnostic armamentarium

“…Having CSF AD biomarkers and other markers such as neurofilament light for distinguishing neurodegenerative from primary psychiatric disorders (Eratne et al, 2022) in the psychiatrist's evaluation 'toolkit', particularly in old-age and consultation-liaison settings, could help improve timely and accurate diagnosis, treatment and outcomes for our patients. As many patients with dementia, especially younger onset, present with psychiatric symptoms, it is important for CSF Alzheimer disease reports detailed levels of amyloid beta 1-42, total tau and phosphorylated tau.…”

“…Cerebrospinal fluid (CSF) analysis is part of the comprehensive multidisciplinary diagnostic workup of possible dementia for patients admitted to Neuropsychiatry, Royal Melbourne Hospital, including AD biomarkers (beta-amyloid 1-42, phosphorylated-tau, total-tau) performed at National Dementia Diagnostics Laboratory, Florey, Melbourne (Eratne et al, 2022). To explore the utility of CSF AD biomarkers for ruling AD in or out (Shaw et al, 2018), and any consequent diagnostic revision in a neuropsychiatry setting, diagnoses were extracted from (1) interim discharge summaries while CSF AD biomarkers results were pending (Pre-CSF Diagnosis) and (2) final discharge summaries, incorporating AD biomarker results (Post-CSF Diagnosis).…”

“…The study is limited by its small sample size and retrospective design, but suggests that CSF Alzheimer biomarkers can add useful information to the challenging diagnosis of cognitive symptoms, especially in younger people. Having CSF AD biomarkers and other markers such as neurofilament light for distinguishing neurodegenerative from primary psychiatric disorders (Eratne et al, 2022) in the psychiatrist’s evaluation ‘toolkit’, particularly in old-age and consultation-liaison settings, could help improve timely and accurate diagnosis, treatment and outcomes for our patients. As many patients with dementia, especially younger onset, present with psychiatric symptoms, it is important for psychiatrists to keep abreast of the rapidly developing biomarker field in the assessment of dementia.…”