scholarly journals CSF Biomarkers Reflecting Protein Pathology and Axonal Degeneration Are Associated with Memory, Attentional, and Executive Functioning in Early-Stage Parkinson′s Disease

2020 ◽  
Vol 21 (22) ◽  
pp. 8519
Author(s):  
Linda P. Oosterveld ◽  
Tessa I. Kuiper ◽  
Nour K. Majbour ◽  
Inge M. W. Verberk ◽  
Karin D. van Dijk ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Executive Functioning ◽  
Light Chain ◽  
Early Stage ◽  
Csf Biomarkers ◽  
Phosphorylated Tau ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Cognitive Domains ◽  
Csf Biomarker

In early-stage Parkinson′s disease (PD), cognitive impairment is common, and a variety of cognitive domains including memory, attention, and executive functioning may be affected. Cerebrospinal fluid (CSF) biomarkers are potential markers of cognitive functioning. We aimed to explore whether CSF α-synuclein species, neurofilament light chain, amyloid-β42, and tau are associated with cognitive performance in early-stage PD patients. CSF levels of total-α-synuclein and phosphorylated-α-synuclein, neurofilament light chain, amyloid-β42, and total-tau and phosphorylated-tau were measured in 26 PD patients (disease duration ≤5 years and Hoehn and Yahr stage 1–2.5). Multivariable linear regression models, adjusted for age, gender, and educational level, were used to assess the relationship between CSF biomarker levels and memory, attention, executive and visuospatial function, and language performance scores. In 26 early-stage PD patients, attention and memory were the most commonly affected domains. A higher CSF phosphorylated-α-synuclein/total-α-synuclein ratio was associated with better executive functioning (sβ = 0.40). Higher CSF neurofilament light was associated with worse memory (sβ = −0.59), attentional (sβ = −0.32), and executive functioning (sβ = −0.35). Reduced CSF amyloid-β42 levels were associated with poorer attentional functioning (sβ = 0.35). Higher CSF phosphorylated-tau was associated with worse language functioning (sβ = −0.33). Thus, CSF biomarker levels, in particular neurofilament light, were related to the most commonly affected cognitive domains in early-stage PD. This indicates that CSF biomarker levels may identify early-stage PD patients who are at an increased risk of developing cognitive impairment.

Cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain predict multiple sclerosis development and disability after optic neuritis

2015 ◽  
Vol 21 (14) ◽  
pp. 1761-1770 ◽  
Author(s):  
S Modvig ◽  
M Degn ◽  
H Roed ◽  
TL Sørensen ◽  
HBW Larsson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Optic Neuritis ◽  
Light Chain ◽  
Oligoclonal Bands ◽  
Enzyme Linked Immunosorbent Assay ◽  
Csf Biomarkers ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Background: Cerebrospinal fluid (CSF) biomarkers have been suggested to predict multiple sclerosis (MS) after clinically isolated syndromes, but studies investigating long-term prognosis are needed. Objective: To assess the predictive ability of CSF biomarkers with regard to MS development and long-term disability after optic neuritis (ON). Methods: Eighty-six patients with ON as a first demyelinating event were included retrospectively. Magnetic resonance imaging (MRI), CSF leukocytes, immunoglobulin G index and oligoclonal bands were registered. CSF levels of chitinase-3-like-1, osteopontin, neurofilament light-chain, myelin basic protein, CCL2, CXCL10, CXCL13 and matrix metalloproteinase-9 were measured by enzyme-linked immunosorbent assay. Patients were followed up after 13.6 (range 9.6–19.4) years and 81.4% were examined, including Expanded Disability Status Scale and MS functional composite evaluation. 18.6% were interviewed by phone. Cox regression, multiple regression and Spearman correlation analyses were used. Results: Forty-six (53.5%) developed clinically definite MS (CDMS) during follow-up. In a multivariate model MRI ( p=0.0001), chitinase 3-like 1 ( p=0.0033) and age ( p=0.0194) combined predicted CDMS best. Neurofilament light-chain predicted long-term disability by the multiple sclerosis severity scale ( p=0.0111) and nine-hole-peg-test ( p=0.0202). Chitinase-3-like-1 predicted long-term cognitive impairment by the paced auditory serial addition test ( p=0.0150). Conclusion: Neurofilament light-chain and chitinase-3-like-1 were significant predictors of long-term physical and cognitive disability. Furthermore, chitinase-3-like-1 predicted CDMS development. Thus, these molecules hold promise as clinically valuable biomarkers after ON as a first demyelinating event.

scholarly journals Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis

2019 ◽  
Vol 266 (9) ◽  
pp. 2157-2163 ◽  
Author(s):  
Lorenzo Gaetani ◽  
Nicola Salvadori ◽  
Viviana Lisetti ◽  
Paolo Eusebi ◽  
Andrea Mancini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Light Chain ◽  
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 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 Peran Neurofilament Light Chain sebagai Biomarker Prediktor Risiko Cognitive Impairment pada Penderita Chronic Kidney Disease

2019 ◽  
Vol 2 (3) ◽  
pp. 7-8
Author(s):  
Nella Rosyalina Damayanti ◽  
Divayari Gardiani
Keyword(s):  
Chronic Kidney Disease ◽  
Cognitive Impairment ◽  
Kidney Disease ◽  
Single Molecule ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Latar Belakang: Chronic Kidney Disease (CKD) dapat menyebabkan cognitive impairment yang dapat menurunkan kualitas hidup dan kesejahteraan emosional pasien. Neurofilament Light Chain (NF-L) merupakan protein yang terletak di aksoplasma yang berperan menjaga struktur neuron. Diskusi: Defisit kognitif yang terjadi pada pasien dengan CKD diakibatkan toksin uremik yang menyebabkan cedera saraf. Prevalensi defisit kognitif berkisar 20-50% pada pasien CKD moderat dan 70% pada pasien CKD berat/ menjalani dialisis. Penurunan fungsi kognitif memiliki korelasi positif dengan penurunan eGFR pada pasien CKD. Kadar NF-L serum ditemukan mengalami peningkatan pada pasien setelah cedera akut pada otak seperti iskemia, perdarahan, dan pada pasien dengan penyakit neurodegeneratif seperti Alzheimer, dibandingkan pada individu sehat. Kadar NF-L serum dapat dideteksi dengan menggunakan pengujian single molecule array (Simoa). Simpulan: Pemeriksaan NF-L dapat dijadikan biomarker terjadinya defisit kognitif pada pasien CKD. Kata Kunci: Chronic Kidney Disease, Neurofilament Light Chain, Fungsi Kognitif, Biomarker

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