Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease
Abstract Background A growing body of evidence suggests that the plasma concentration of the neurofilament light chain (NfL) might be considered a plasma biomarker for the screening of neurodegeneration in Alzheimer’s disease (AD). Methods With a single molecule array method (Simoa, Quanterix), plas...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-07-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13195-018-0404-9 |
| _version_ | 1818290081202438144 |
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| author | Piotr Lewczuk Natalia Ermann Ulf Andreasson Christian Schultheis Jana Podhorna Philipp Spitzer Juan Manuel Maler Johannes Kornhuber Kaj Blennow Henrik Zetterberg |
| author_facet | Piotr Lewczuk Natalia Ermann Ulf Andreasson Christian Schultheis Jana Podhorna Philipp Spitzer Juan Manuel Maler Johannes Kornhuber Kaj Blennow Henrik Zetterberg |
| author_sort | Piotr Lewczuk |
| collection | DOAJ |
| description | Abstract Background A growing body of evidence suggests that the plasma concentration of the neurofilament light chain (NfL) might be considered a plasma biomarker for the screening of neurodegeneration in Alzheimer’s disease (AD). Methods With a single molecule array method (Simoa, Quanterix), plasma NfL concentrations were measured in 99 subjects with AD at the stage of mild cognitive impairment (MCI-AD; n = 25) or at the stage of early dementia (ADD; n = 33), and in nondemented controls (n = 41); in all patients, the clinical diagnoses were in accordance with the results of the four core cerebrospinal fluid (CSF) biomarkers (amyloid β (Aβ)1–42, Aβ42/40, Tau, and pTau181), interpreted according to the Erlangen Score algorithm. The influence of preanalytical storage procedures on the NfL in plasma was tested on samples exposed to six different conditions. Results NfL concentrations significantly increased in the samples exposed to more than one freezing/thawing cycle, and in those stored for 5 days at room temperature or at 4 °C. Compared with the control group of nondemented subjects (22.0 ± 12.4 pg/mL), the unadjusted plasma NfL concentration was highly significantly higher in the MCI-AD group (38.1 ± 15.9 pg/mL, p < 0.005) and even further elevated in the ADD group (49.1 ± 28.4 pg/mL; p < 0.001). A significant association between NfL and age (ρ = 0.65, p < 0.001) was observed; after correcting for age, the difference in NfL concentrations between AD and controls remained significant (p = 0.044). At the cutoff value of 25.7 pg/mL, unconditional sensitivity, specificity, and accuracy were 0.84, 0.78, and 0.82, respectively. Unadjusted correlation between plasma NfL and Mini Mental State Examination (MMSE) across all patients was moderate but significant (r = −0.49, p < 0.001). We observed an overall significant correlation between plasma NfL and the CSF biomarkers, but this correlation was not observed within the diagnostic groups. Conclusions This study confirms increased concentrations of plasma NfL in patients with Alzheimer’s disease compared with nondemented controls. |
| first_indexed | 2024-12-13T02:22:30Z |
| format | Article |
| id | doaj.art-0cd63c9daa4e4d9b946bab44c4175f96 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-12-13T02:22:30Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-0cd63c9daa4e4d9b946bab44c4175f962022-12-22T00:02:43ZengBMCAlzheimer’s Research & Therapy1758-91932018-07-0110111010.1186/s13195-018-0404-9Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s diseasePiotr Lewczuk0Natalia Ermann1Ulf Andreasson2Christian Schultheis3Jana Podhorna4Philipp Spitzer5Juan Manuel Maler6Johannes Kornhuber7Kaj Blennow8Henrik Zetterberg9Department of Psychiatry and Psychotherapy, Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-NürnbergDepartment of Psychiatry and Psychotherapy, Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-NürnbergClinical Neurochemistry Laboratory, Sahlgrenska University HospitalBoehringer Ingelheim Pharma GmbH & Co. KGBoehringer Ingelheim International GmbHDepartment of Psychiatry and Psychotherapy, Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-NürnbergDepartment of Psychiatry and Psychotherapy, Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-NürnbergDepartment of Psychiatry and Psychotherapy, Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-NürnbergClinical Neurochemistry Laboratory, Sahlgrenska University HospitalClinical Neurochemistry Laboratory, Sahlgrenska University HospitalAbstract Background A growing body of evidence suggests that the plasma concentration of the neurofilament light chain (NfL) might be considered a plasma biomarker for the screening of neurodegeneration in Alzheimer’s disease (AD). Methods With a single molecule array method (Simoa, Quanterix), plasma NfL concentrations were measured in 99 subjects with AD at the stage of mild cognitive impairment (MCI-AD; n = 25) or at the stage of early dementia (ADD; n = 33), and in nondemented controls (n = 41); in all patients, the clinical diagnoses were in accordance with the results of the four core cerebrospinal fluid (CSF) biomarkers (amyloid β (Aβ)1–42, Aβ42/40, Tau, and pTau181), interpreted according to the Erlangen Score algorithm. The influence of preanalytical storage procedures on the NfL in plasma was tested on samples exposed to six different conditions. Results NfL concentrations significantly increased in the samples exposed to more than one freezing/thawing cycle, and in those stored for 5 days at room temperature or at 4 °C. Compared with the control group of nondemented subjects (22.0 ± 12.4 pg/mL), the unadjusted plasma NfL concentration was highly significantly higher in the MCI-AD group (38.1 ± 15.9 pg/mL, p < 0.005) and even further elevated in the ADD group (49.1 ± 28.4 pg/mL; p < 0.001). A significant association between NfL and age (ρ = 0.65, p < 0.001) was observed; after correcting for age, the difference in NfL concentrations between AD and controls remained significant (p = 0.044). At the cutoff value of 25.7 pg/mL, unconditional sensitivity, specificity, and accuracy were 0.84, 0.78, and 0.82, respectively. Unadjusted correlation between plasma NfL and Mini Mental State Examination (MMSE) across all patients was moderate but significant (r = −0.49, p < 0.001). We observed an overall significant correlation between plasma NfL and the CSF biomarkers, but this correlation was not observed within the diagnostic groups. Conclusions This study confirms increased concentrations of plasma NfL in patients with Alzheimer’s disease compared with nondemented controls.http://link.springer.com/article/10.1186/s13195-018-0404-9Alzheimer’s diseaseNeurofilament lightBiomarkerPlasma |
| spellingShingle | Piotr Lewczuk Natalia Ermann Ulf Andreasson Christian Schultheis Jana Podhorna Philipp Spitzer Juan Manuel Maler Johannes Kornhuber Kaj Blennow Henrik Zetterberg Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease Alzheimer’s Research & Therapy Alzheimer’s disease Neurofilament light Biomarker Plasma |
| title | Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease |
| title_full | Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease |
| title_fullStr | Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease |
| title_full_unstemmed | Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease |
| title_short | Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease |
| title_sort | plasma neurofilament light as a potential biomarker of neurodegeneration in alzheimer s disease |
| topic | Alzheimer’s disease Neurofilament light Biomarker Plasma |
| url | http://link.springer.com/article/10.1186/s13195-018-0404-9 |
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