Cerebrospinal fluid neurofilament light concentration predicts brain atrophy and cognition in Alzheimer's disease

Kunal Dhiman; Veer Bala Gupta; Victor L. Villemagne; Dhamidhu Eratne; Petra L. Graham; Christopher Fowler; Pierrick Bourgeat; Qiao-Xin Li; Steven Collins; Ashley I. Bush; Christopher C. Rowe; Colin L. Masters; David Ames; Eugene Hone; Kaj Blennow; Henrik Zetterberg; Ralph N. Martins

doi:10.1002/dad2.12005

Cerebrospinal fluid neurofilament light concentration predicts brain atrophy and cognition in Alzheimer's disease

Kunal Dhiman, Veer Bala Gupta^*, Victor L. Villemagne, Dhamidhu Eratne, Petra L. Graham, Christopher Fowler, Pierrick Bourgeat, Qiao-Xin Li, Steven Collins, Ashley I. Bush, Christopher C. Rowe, Colin L. Masters, David Ames, Eugene Hone, Kaj Blennow, Henrik Zetterberg, Ralph N. Martins

^*Corresponding author for this work

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Abstract

Introduction: This study assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) in Alzheimer's disease (AD) diagnosis, its association with amyloid and tau pathology, as well as its potential to predict brain atrophy, cognition, and amyloid accumulation.

Methods: CSF NfL concentration was measured in 221 participants from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL).

Results: CSF NfL levels as well as NfL/amyloid β (Aβ42) were significantly elevated in AD compared to healthy controls (HC; P <.001), and in mild cognitive impairment (MCI) compared to HC (P =.008 NfL; P <.001 NfL/Aβ42). CSF NfL and NfL/Aβ42 differentiated AD from HC with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.84 and 0.90, respectively. CSF NfL and NfL/Aβ42 predicted cortical amyloid load, brain atrophy, and cognition.

Discussion: CSF NfL is a biomarker of neurodegeneration, correlating with cognitive impairment and brain neuropathology.

Original language	English
Article number	e12005
Pages (from-to)	1-9
Number of pages	9
Journal	Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume	12
Issue number	1
DOIs	https://doi.org/10.1002/dad2.12005
Publication status	Published - 27 Feb 2020

Bibliographical note

Copyright 2020 The Authors. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of the Alzheimer’s Association. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

amyloid
biomarker
dementia
diagnosis
ELISA
neurodegeneration
neurofilaments

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Dhiman, K., Gupta, V. B., Villemagne, V. L., Eratne, D., Graham, P. L., Fowler, C., Bourgeat, P., Li, Q-X., Collins, S., Bush, A. I., Rowe, C. C., Masters, C. L., Ames, D., Hone, E., Blennow, K., Zetterberg, H., & Martins, R. N. (2020). Cerebrospinal fluid neurofilament light concentration predicts brain atrophy and cognition in Alzheimer's disease. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 12(1), 1-9. [e12005]. https://doi.org/10.1002/dad2.12005

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title = "Cerebrospinal fluid neurofilament light concentration predicts brain atrophy and cognition in Alzheimer's disease",

abstract = "Introduction: This study assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) in Alzheimer's disease (AD) diagnosis, its association with amyloid and tau pathology, as well as its potential to predict brain atrophy, cognition, and amyloid accumulation.Methods: CSF NfL concentration was measured in 221 participants from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL).Results: CSF NfL levels as well as NfL/amyloid β (Aβ42) were significantly elevated in AD compared to healthy controls (HC; P <.001), and in mild cognitive impairment (MCI) compared to HC (P =.008 NfL; P <.001 NfL/Aβ42). CSF NfL and NfL/Aβ42 differentiated AD from HC with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.84 and 0.90, respectively. CSF NfL and NfL/Aβ42 predicted cortical amyloid load, brain atrophy, and cognition.Discussion: CSF NfL is a biomarker of neurodegeneration, correlating with cognitive impairment and brain neuropathology.",

keywords = "amyloid, biomarker, dementia, diagnosis, ELISA, neurodegeneration, neurofilaments",

author = "Kunal Dhiman and Gupta, {Veer Bala} and Villemagne, {Victor L.} and Dhamidhu Eratne and Graham, {Petra L.} and Christopher Fowler and Pierrick Bourgeat and Qiao-Xin Li and Steven Collins and Bush, {Ashley I.} and Rowe, {Christopher C.} and Masters, {Colin L.} and David Ames and Eugene Hone and Kaj Blennow and Henrik Zetterberg and Martins, {Ralph N.}",

note = "Copyright 2020 The Authors. Alzheimer{\textquoteright}s & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of the Alzheimer{\textquoteright}s Association. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2020",

month = feb,

day = "27",

doi = "10.1002/dad2.12005",

language = "English",

volume = "12",

pages = "1--9",

journal = "Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring",

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Dhiman, K, Gupta, VB, Villemagne, VL, Eratne, D, Graham, PL, Fowler, C, Bourgeat, P, Li, Q-X, Collins, S, Bush, AI, Rowe, CC, Masters, CL, Ames, D, Hone, E, Blennow, K, Zetterberg, H & Martins, RN 2020, 'Cerebrospinal fluid neurofilament light concentration predicts brain atrophy and cognition in Alzheimer's disease', Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, vol. 12, no. 1, e12005, pp. 1-9. https://doi.org/10.1002/dad2.12005

TY - JOUR

T1 - Cerebrospinal fluid neurofilament light concentration predicts brain atrophy and cognition in Alzheimer's disease

AU - Dhiman, Kunal

AU - Gupta, Veer Bala

AU - Villemagne, Victor L.

AU - Eratne, Dhamidhu

AU - Graham, Petra L.

AU - Fowler, Christopher

AU - Bourgeat, Pierrick

AU - Li, Qiao-Xin

AU - Collins, Steven

AU - Bush, Ashley I.

AU - Rowe, Christopher C.

AU - Masters, Colin L.

AU - Ames, David

AU - Hone, Eugene

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Martins, Ralph N.

N1 - Copyright 2020 The Authors. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of the Alzheimer’s Association. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2020/2/27

Y1 - 2020/2/27

N2 - Introduction: This study assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) in Alzheimer's disease (AD) diagnosis, its association with amyloid and tau pathology, as well as its potential to predict brain atrophy, cognition, and amyloid accumulation.Methods: CSF NfL concentration was measured in 221 participants from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL).Results: CSF NfL levels as well as NfL/amyloid β (Aβ42) were significantly elevated in AD compared to healthy controls (HC; P <.001), and in mild cognitive impairment (MCI) compared to HC (P =.008 NfL; P <.001 NfL/Aβ42). CSF NfL and NfL/Aβ42 differentiated AD from HC with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.84 and 0.90, respectively. CSF NfL and NfL/Aβ42 predicted cortical amyloid load, brain atrophy, and cognition.Discussion: CSF NfL is a biomarker of neurodegeneration, correlating with cognitive impairment and brain neuropathology.

AB - Introduction: This study assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) in Alzheimer's disease (AD) diagnosis, its association with amyloid and tau pathology, as well as its potential to predict brain atrophy, cognition, and amyloid accumulation.Methods: CSF NfL concentration was measured in 221 participants from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL).Results: CSF NfL levels as well as NfL/amyloid β (Aβ42) were significantly elevated in AD compared to healthy controls (HC; P <.001), and in mild cognitive impairment (MCI) compared to HC (P =.008 NfL; P <.001 NfL/Aβ42). CSF NfL and NfL/Aβ42 differentiated AD from HC with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.84 and 0.90, respectively. CSF NfL and NfL/Aβ42 predicted cortical amyloid load, brain atrophy, and cognition.Discussion: CSF NfL is a biomarker of neurodegeneration, correlating with cognitive impairment and brain neuropathology.

KW - amyloid

KW - biomarker

KW - dementia

KW - diagnosis

KW - ELISA

KW - neurodegeneration

KW - neurofilaments

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U2 - 10.1002/dad2.12005

DO - 10.1002/dad2.12005

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C2 - 32211500

AN - SCOPUS:85080986432

VL - 12

SP - 1

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JO - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring

JF - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring

SN - 2352-8729

IS - 1

M1 - e12005

ER -

Cerebrospinal fluid neurofilament light concentration predicts brain atrophy and cognition in Alzheimer's disease

Abstract

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