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Plasma tau, neurofilament light chain and amyloid-b levels and risk of dementia; a population-based cohort study. / de Wolf, Frank; Ghanbari, Mohsen; Licher, Silvan et al.

In: Brain, Vol. 143, No. 3, 01.03.2020, p. 1220-1232.

Research output: Contribution to journalArticleAcademicpeer-review

Harvard

de Wolf, F, Ghanbari, M, Licher, S, McRae-McKee, K, Gras, L, Weverling, GJ, Wermeling, P, Sedaghat, S, Kamran Ikram, M, Waziry, R, Koudstaal, W, Klap, J, Kostense, S, Hofman, A, Anderson, R, Goudsmit, J & Arfan Ikram, M 2020, 'Plasma tau, neurofilament light chain and amyloid-b levels and risk of dementia; a population-based cohort study', Brain, vol. 143, no. 3, pp. 1220-1232. https://doi.org/10.1093/brain/awaa054

APA

de Wolf, F., Ghanbari, M., Licher, S., McRae-McKee, K., Gras, L., Weverling, G. J., Wermeling, P., Sedaghat, S., Kamran Ikram, M., Waziry, R., Koudstaal, W., Klap, J., Kostense, S., Hofman, A., Anderson, R., Goudsmit, J., & Arfan Ikram, M. (2020). Plasma tau, neurofilament light chain and amyloid-b levels and risk of dementia; a population-based cohort study. Brain, 143(3), 1220-1232. https://doi.org/10.1093/brain/awaa054

Vancouver

de Wolf F, Ghanbari M, Licher S, McRae-McKee K, Gras L, Weverling GJ et al. Plasma tau, neurofilament light chain and amyloid-b levels and risk of dementia; a population-based cohort study. Brain. 2020 Mar 1;143(3):1220-1232. doi: 10.1093/brain/awaa054

Author

de Wolf, Frank ; Ghanbari, Mohsen ; Licher, Silvan et al. / Plasma tau, neurofilament light chain and amyloid-b levels and risk of dementia; a population-based cohort study. In: Brain. 2020 ; Vol. 143, No. 3. pp. 1220-1232.

BibTeX

@article{ddf341465a8d45549db63dcc35cea857,
title = "Plasma tau, neurofilament light chain and amyloid-b levels and risk of dementia; a population-based cohort study",
abstract = "CSF biomarkers, including total-tau, neurofilament light chain (NfL) and amyloid-b, are increasingly being used to define and stage Alzheimer's disease. These biomarkers can be measured more quickly and less invasively in plasma and may provide important information for early diagnosis of Alzheimer's disease. We used stored plasma samples and clinical data obtained from 4444 non-demented participants in the Rotterdam study at baseline (between 2002 and 2005) and during follow-up until January 2016. Plasma concentrations of total-tau, NfL, amyloid-b40 and amyloid-b42 were measured using the Simoa NF-lightVR and N3PA assays. Associations between biomarker plasma levels and incident all-cause and Alzheimer's disease dementia during follow-up were assessed using Cox proportional-hazard regression models adjusted for age, sex, education, cardiovascular risk factors and APOE e4 status. Moreover, biomarker plasma levels and rates of change over time of participants who developed Alzheimer's disease dementia during follow-up were compared with age and sex-matched dementia-free control subjects. During up to 14 years follow-up, 549 participants developed dementia, including 374 cases with Alzheimer's disease dementia. A log2 higher baseline amyloid-b42 plasma level was associated with a lower risk of developing all-cause or Alzheimer's disease dementia, adjusted hazard ratio (HR) 0.61 [95% confidence interval (CI), 0.47-0.78; P 5 0.0001] and 0.59 (95% CI, 0.43-0.79; P = 0.0006), respectively. Conversely, a log2 higher baseline plasma NfL level was associated with a higher risk of all-cause dementia [adjusted HR 1.59 (95% CI, 1.38-1.83); P 5 0.0001] or Alzheimer's disease [adjusted HR 1.50 (95% CI, 1.26-1.78); P 5 0.0001]. Combining the lowest quartile group of amyloid-b42 with the highest of NfL resulted in a stronger association with all-cause dementia [adjusted HR 9.5 (95% CI, 2.3-40.4); P 5 0.002] and with Alzheimer's disease [adjusted HR 15.7 (95% CI, 2.1-117.4); P 5 0.0001], compared to the highest quartile group of amyloid-b42 and lowest of NfL. Total-tau and amyloid-b40 levels were not associated with all-cause or Alzheimer's disease dementia risk. Trajectory analyses of biomarkers revealed that mean NfL plasma levels increased 3.4 times faster in participants who developed Alzheimer's disease compared to those who remained dementia-free (P 5 0.0001), plasma values for cases diverged from controls 9.6 years before Alzheimer's disease diagnosis. Amyloid-b42 levels began to decrease in Alzheimer's disease cases a few years before diagnosis, although the decline did not reach significance compared to dementia-free participants. In conclusion, our study shows that low amyloid-b42 and high NfL plasma levels are each independently and in combination strongly associated with risk of all-cause and Alzheimer's disease dementia. These data indicate that plasma NfL and amyloid-b42 levels can be used to assess the risk of developing dementia in a non-demented population. Plasma NfL levels, although not specific, may also be useful in monitoring progression of Alzheimer's disease dementia.",
keywords = "Ab42, Alzheimer's disease, Dementia, NfL, Plasma biomarkers",
author = "{de Wolf}, Frank and Mohsen Ghanbari and Silvan Licher and Kevin McRae-McKee and Luuk Gras and Weverling, {Gerrit Jan} and Paulien Wermeling and Sanaz Sedaghat and {Kamran Ikram}, M. and Reem Waziry and Wouter Koudstaal and Jaco Klap and Stefan Kostense and Albert Hofman and Roy Anderson and Jaap Goudsmit and {Arfan Ikram}, M.",
year = "2020",
month = mar,
day = "1",
doi = "10.1093/brain/awaa054",
language = "English",
volume = "143",
pages = "1220--1232",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "3",

}

RIS

TY - JOUR

T1 - Plasma tau, neurofilament light chain and amyloid-b levels and risk of dementia; a population-based cohort study

AU - de Wolf, Frank

AU - Ghanbari, Mohsen

AU - Licher, Silvan

AU - McRae-McKee, Kevin

AU - Gras, Luuk

AU - Weverling, Gerrit Jan

AU - Wermeling, Paulien

AU - Sedaghat, Sanaz

AU - Kamran Ikram, M.

AU - Waziry, Reem

AU - Koudstaal, Wouter

AU - Klap, Jaco

AU - Kostense, Stefan

AU - Hofman, Albert

AU - Anderson, Roy

AU - Goudsmit, Jaap

AU - Arfan Ikram, M.

PY - 2020/3/1

Y1 - 2020/3/1

N2 - CSF biomarkers, including total-tau, neurofilament light chain (NfL) and amyloid-b, are increasingly being used to define and stage Alzheimer's disease. These biomarkers can be measured more quickly and less invasively in plasma and may provide important information for early diagnosis of Alzheimer's disease. We used stored plasma samples and clinical data obtained from 4444 non-demented participants in the Rotterdam study at baseline (between 2002 and 2005) and during follow-up until January 2016. Plasma concentrations of total-tau, NfL, amyloid-b40 and amyloid-b42 were measured using the Simoa NF-lightVR and N3PA assays. Associations between biomarker plasma levels and incident all-cause and Alzheimer's disease dementia during follow-up were assessed using Cox proportional-hazard regression models adjusted for age, sex, education, cardiovascular risk factors and APOE e4 status. Moreover, biomarker plasma levels and rates of change over time of participants who developed Alzheimer's disease dementia during follow-up were compared with age and sex-matched dementia-free control subjects. During up to 14 years follow-up, 549 participants developed dementia, including 374 cases with Alzheimer's disease dementia. A log2 higher baseline amyloid-b42 plasma level was associated with a lower risk of developing all-cause or Alzheimer's disease dementia, adjusted hazard ratio (HR) 0.61 [95% confidence interval (CI), 0.47-0.78; P 5 0.0001] and 0.59 (95% CI, 0.43-0.79; P = 0.0006), respectively. Conversely, a log2 higher baseline plasma NfL level was associated with a higher risk of all-cause dementia [adjusted HR 1.59 (95% CI, 1.38-1.83); P 5 0.0001] or Alzheimer's disease [adjusted HR 1.50 (95% CI, 1.26-1.78); P 5 0.0001]. Combining the lowest quartile group of amyloid-b42 with the highest of NfL resulted in a stronger association with all-cause dementia [adjusted HR 9.5 (95% CI, 2.3-40.4); P 5 0.002] and with Alzheimer's disease [adjusted HR 15.7 (95% CI, 2.1-117.4); P 5 0.0001], compared to the highest quartile group of amyloid-b42 and lowest of NfL. Total-tau and amyloid-b40 levels were not associated with all-cause or Alzheimer's disease dementia risk. Trajectory analyses of biomarkers revealed that mean NfL plasma levels increased 3.4 times faster in participants who developed Alzheimer's disease compared to those who remained dementia-free (P 5 0.0001), plasma values for cases diverged from controls 9.6 years before Alzheimer's disease diagnosis. Amyloid-b42 levels began to decrease in Alzheimer's disease cases a few years before diagnosis, although the decline did not reach significance compared to dementia-free participants. In conclusion, our study shows that low amyloid-b42 and high NfL plasma levels are each independently and in combination strongly associated with risk of all-cause and Alzheimer's disease dementia. These data indicate that plasma NfL and amyloid-b42 levels can be used to assess the risk of developing dementia in a non-demented population. Plasma NfL levels, although not specific, may also be useful in monitoring progression of Alzheimer's disease dementia.

AB - CSF biomarkers, including total-tau, neurofilament light chain (NfL) and amyloid-b, are increasingly being used to define and stage Alzheimer's disease. These biomarkers can be measured more quickly and less invasively in plasma and may provide important information for early diagnosis of Alzheimer's disease. We used stored plasma samples and clinical data obtained from 4444 non-demented participants in the Rotterdam study at baseline (between 2002 and 2005) and during follow-up until January 2016. Plasma concentrations of total-tau, NfL, amyloid-b40 and amyloid-b42 were measured using the Simoa NF-lightVR and N3PA assays. Associations between biomarker plasma levels and incident all-cause and Alzheimer's disease dementia during follow-up were assessed using Cox proportional-hazard regression models adjusted for age, sex, education, cardiovascular risk factors and APOE e4 status. Moreover, biomarker plasma levels and rates of change over time of participants who developed Alzheimer's disease dementia during follow-up were compared with age and sex-matched dementia-free control subjects. During up to 14 years follow-up, 549 participants developed dementia, including 374 cases with Alzheimer's disease dementia. A log2 higher baseline amyloid-b42 plasma level was associated with a lower risk of developing all-cause or Alzheimer's disease dementia, adjusted hazard ratio (HR) 0.61 [95% confidence interval (CI), 0.47-0.78; P 5 0.0001] and 0.59 (95% CI, 0.43-0.79; P = 0.0006), respectively. Conversely, a log2 higher baseline plasma NfL level was associated with a higher risk of all-cause dementia [adjusted HR 1.59 (95% CI, 1.38-1.83); P 5 0.0001] or Alzheimer's disease [adjusted HR 1.50 (95% CI, 1.26-1.78); P 5 0.0001]. Combining the lowest quartile group of amyloid-b42 with the highest of NfL resulted in a stronger association with all-cause dementia [adjusted HR 9.5 (95% CI, 2.3-40.4); P 5 0.002] and with Alzheimer's disease [adjusted HR 15.7 (95% CI, 2.1-117.4); P 5 0.0001], compared to the highest quartile group of amyloid-b42 and lowest of NfL. Total-tau and amyloid-b40 levels were not associated with all-cause or Alzheimer's disease dementia risk. Trajectory analyses of biomarkers revealed that mean NfL plasma levels increased 3.4 times faster in participants who developed Alzheimer's disease compared to those who remained dementia-free (P 5 0.0001), plasma values for cases diverged from controls 9.6 years before Alzheimer's disease diagnosis. Amyloid-b42 levels began to decrease in Alzheimer's disease cases a few years before diagnosis, although the decline did not reach significance compared to dementia-free participants. In conclusion, our study shows that low amyloid-b42 and high NfL plasma levels are each independently and in combination strongly associated with risk of all-cause and Alzheimer's disease dementia. These data indicate that plasma NfL and amyloid-b42 levels can be used to assess the risk of developing dementia in a non-demented population. Plasma NfL levels, although not specific, may also be useful in monitoring progression of Alzheimer's disease dementia.

KW - Ab42

KW - Alzheimer's disease

KW - Dementia

KW - NfL

KW - Plasma biomarkers

UR - http://www.scopus.com/inward/record.url?scp=85088631757&partnerID=8YFLogxK

U2 - 10.1093/brain/awaa054

DO - 10.1093/brain/awaa054

M3 - Article

C2 - 32206776

VL - 143

SP - 1220

EP - 1232

JO - Brain

JF - Brain

SN - 0006-8950

IS - 3

ER -

ID: 13281271