scholarly journals CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP

Neurology ◽  
2017 ◽  
Vol 90 (4) ◽  
pp. e273-e281 ◽  
Author(s):  
Julio C. Rojas ◽  
Jee Bang ◽  
Iryna V. Lobach ◽  
Richard M. Tsai ◽  
Gil D. Rabinovici ◽  
...  
Keyword(s):  
Disease Progression ◽  
Disease Severity ◽  
Light Chain ◽  
Rating Scale ◽  
Superior Cerebellar Peduncle ◽  
Phosphorylated Tau ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Phosphorylated Tau 181 ◽  
Predict Disease Progression

ObjectiveTo determine the ability of CSF biomarkers to predict disease progression in progressive supranuclear palsy (PSP).MethodsWe compared the ability of baseline CSF β-amyloid1–42, tau, phosphorylated tau 181 (p-tau), and neurofilament light chain (NfL) concentrations, measured by INNO-BIA AlzBio3 or ELISA, to predict 52-week changes in clinical (PSP Rating Scale [PSPRS] and Schwab and England Activities of Daily Living [SEADL]), neuropsychological, and regional brain volumes on MRI using linear mixed effects models controlled for age, sex, and baseline disease severity, and Fisher F density curves to compare effect sizes in 50 patients with PSP. Similar analyses were done using plasma NfL measured by single molecule arrays in 141 patients.ResultsHigher CSF NfL concentration predicted more rapid decline (biomarker × time interaction) over 52 weeks in PSPRS (p = 0.004, false discovery rate–corrected) and SEADL (p = 0.008), whereas lower baseline CSF p-tau predicted faster decline on PSPRS (p = 0.004). Higher CSF tau concentrations predicted faster decline by SEADL (p = 0.004). The CSF NfL/p-tau ratio was superior for predicting change in PSPRS, compared to p-tau (p = 0.003) or NfL (p = 0.001) alone. Higher NfL concentrations in CSF or blood were associated with greater superior cerebellar peduncle atrophy (fixed effect, p ≤ 0.029 and 0.008, respectively).ConclusionsBoth CSF p-tau and NfL correlate with disease severity and rate of disease progression in PSP. The inverse correlation of p-tau with disease severity suggests a potentially different mechanism of tau pathology in PSP as compared to Alzheimer disease.

P3-251: SERUM NEUROFILAMENT LIGHT CHAIN LEVELS ARE ASSOCIATED WITH CSF NEUROFILAMENT LIGHT CHAIN, COGNITIVE STATUS, AND DISEASE PROGRESSION IN AUTOSOMAL DOMINANT AD

2006 ◽  
Vol 14 (7S_Part_22) ◽  
pp. P1170-P1170 ◽  
Author(s):  
Oliver Preische ◽  
Stephanie A. Schultz ◽  
Anja Apel ◽  
Jens Kuhle ◽  
Brian A. Gordon ◽  
...  
Keyword(s):  
Disease Progression ◽  
Light Chain ◽  
Autosomal Dominant ◽  
Cognitive Status ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Temporal Correlation of CSF and Neuroimaging in the Amyloid-Tau-Neurodegeneration Model of Alzheimer Disease

Neurology ◽  
2021 ◽  
Author(s):  
Anna H. Boerwinkle ◽  
Julie K. Wisch ◽  
Charles D. Chen ◽  
Brian A. Gordon ◽  
Omar Hameed Butt ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Cortical Thickness ◽  
Light Chain ◽  
Amyloid Β ◽  
Time Interval ◽  
Phosphorylated Tau ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Total Tau ◽  
Maximal Correlation

Objective:Temporal correlations between CSF and neuroimaging (PET and MRI) measures of amyloid, tau, and neurodegeneration were evaluated in relation to Alzheimer disease (AD) progression.Methods:Three hundred seventy-one cognitively unimpaired and impaired participants enrolled in longitudinal studies of AD had both CSF (amyloid-β42, phosphorylated tau181, total tau, and neurofilament light chain) and neuroimaging (PiB PET, flortaucipir PET, and structural MRI) measures. The pairwise time interval between CSF and neuroimaging measures was binned into two year periods. Spearman correlations identified the time bin when CSF and neuroimaging measures most strongly correlated. CSF and neuroimaging measures were then binarized as biomarker-positive or biomarker-negative using Gaussian mixture modelling. Cohen’s kappa coefficient identified the time bin when CSF measures best agreed with corresponding neuroimaging measures when determining amyloid, tau, and neurodegeneration biomarker positivity.Results:CSF amyloid-β42 and PiB PET showed maximal correlation when collected within six years of each other (R ≈ -0.5). CSF phosphorylated tau181 and flortaucipir PET showed maximal correlation when CSF was collected four to eight years prior to PET (R ≈ 0.4). CSF neurofilament light chain and cortical thickness showed low correlation, regardless of time interval (Ravg ≈ -0.3). Similarly, CSF total tau and cortical thickness had low correlation, regardless of time interval (Ravg < -0.2).Conclusions:CSF amyloid-β42 and PiB PET best agree when acquired in close temporal proximity, whereas CSF phosphorylated tau precedes flortaucipir PET by four to eight years. CSF and neuroimaging measures of neurodegeneration have low correspondence and are not interchangeable at any time interval.

scholarly journals Plasma Neurofilament Light Chain Predicts Cognitive Progression in Prodromal and Clinical Dementia with Lewy Bodies

2021 ◽  
pp. 1-7
Author(s):  
Andrea Pilotto ◽  
Alberto Imarisio ◽  
Claudia Carrarini ◽  
Mirella Russo ◽  
Stefano Masciocchi ◽  
...  
Keyword(s):  
Light Chain ◽  
Neurological Disorders ◽  
Dementia With Lewy Bodies ◽  
Neuronal Damage ◽  
Lewy Bodies ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Predict Disease Progression

Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients (including 17 prodromal cases) who underwent an extensive assessment at baseline and at 2 years follow-up. At baseline, plasma NfL levels were higher in both probable DLB and prodromal cases compared to controls. Plasma NfL emerged as the best predictor of cognitive decline compared to age, sex, and baseline severity variables. The study supports the role of plasma NfL as a useful prognostic biomarker from the early stages of DLB.

scholarly journals Plasma neurofilament light and phosphorylated tau 181 as biomarkers of Alzheimer’s disease pathology and clinical disease progression

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Christopher Clark ◽  
Piotr Lewczuk ◽  
Johannes Kornhuber ◽  
Jonas Richiardi ◽  
Bénédicte Maréchal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Disease Progression ◽  
Reference Model ◽  
Csf Biomarkers ◽  
Phosphorylated Tau ◽  
Memory Clinic ◽  
Neurofilament Light ◽  
Phosphorylated Tau 181

Abstract Background To assess the performance of plasma neurofilament light (NfL) and phosphorylated tau 181 (p-tau181) to inform about cerebral Alzheimer’s disease (AD) pathology and predict clinical progression in a memory clinic setting. Methods Plasma NfL and p-tau181, along with established cerebrospinal fluid (CSF) biomarkers of AD pathology, were measured in participants with normal cognition (CN) and memory clinic patients with cognitive impairment (mild cognitive impairment and dementia, CI). Clinical and neuropsychological assessments were performed at inclusion and follow-up visits at 18 and 36 months. Multivariate analysis assessed associations of plasma NfL and p-tau181 levels with AD, single CSF biomarkers, hippocampal volume, and clinical measures of disease progression. Results Plasma NfL levels were higher in CN participants with an AD CSF profile (defined by a CSF p-tau181/Aβ1–42 > 0.0779) as compared with CN non-AD, while p-tau181 plasma levels were higher in CI patients with AD. Plasma NfL levels correlated with CSF tau and p-tau181 in CN, and with CSF tau in CI patients. Plasma p-tau181 correlated with CSF p-tau181 in CN and with CSF tau, p-tau181, Aβ1–42, and Aβ1–42/Aβ1–40 in CI participants. Compared with a reference model, adding plasma p-tau181 improved the prediction of AD in CI patients while adding NfL did not. Adding p-tau181, but not NfL levels, to a reference model improved prediction of cognitive decline in CI participants. Conclusion Plasma NfL indicates neurodegeneration while plasma p-tau181 levels can serve as a biomarker of cerebral AD pathology and cognitive decline. Their predictive performance depends on the presence of cognitive impairment.

scholarly journals Plasma Neurofilament Light Chain predicts cognitive progression in prodromal and clinical dementia with Lewy Bodies

2021 ◽  
Author(s):  
Andrea Pilotto ◽  
Alberto Imarisio ◽  
Claudia Carrarini ◽  
Mirella Russo ◽  
Stefano Masciocchi ◽  
...  
Keyword(s):  
Light Chain ◽  
Neurological Disorders ◽  
Dementia With Lewy Bodies ◽  
Neuronal Damage ◽  
Lewy Bodies ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Predict Disease Progression

Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients (including 17 prodromal cases) who underwent an extensive assessment at baseline and at 2 years follow-up. At baseline, plasma NfL levels were higher in both probable DLB and prodromal cases compared to controls. Plasma NfL emerged as the best predictor of cognitive decline compared to age, sex and baseline severity variables. The study supports the role of plasma NfL as a useful prognostic biomarker from the early stages of DLB.

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