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Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer's disease

Artikel i vetenskaplig tidskrift
Författare P. Lewczuk
N. Ermann
Ulf Andreasson
C. Schultheis
J. Podhorna
P. Spitzer
J. M. Maler
J. Kornhuber
Kaj Blennow
Henrik Zetterberg
Publicerad i Alzheimers Research & Therapy
Volym 10
Nummer/häfte 71
ISSN 1758-9193
Publiceringsår 2018
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Språk en
Länkar dx.doi.org/10.1186/s13195-018-0404-...
Ämnesord Alzheimer's disease, Neurofilament light, Biomarker, Plasma, neurochemical dementia diagnostics, cerebrospinal-fluid, association, workgroups, hypothetical model, national institute, dynamic biomarkers, blood biomarkers, chain protein, marker, csf, Neurosciences & Neurology
Ämneskategorier Neurokemi

Sammanfattning

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 beta (A beta) 1-42, A beta 42/40, 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 degrees 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 (p = 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.

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