Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum

Isabelle Bos; Stephanie Vos; Frans Verhey; Philip Scheltens; Charlotte Teunissen; Sebastiaan Engelborghs; Kristel Sleegers; Giovanni Frisoni; Olivier Blin; Jill C Richardson; Régis Bordet; Magda Tsolaki; Julius Popp; Gwendoline Peyratout; Pablo Martinez-Lage; Mikel Tainta; Alberto Lleó; Peter Johannsen; Yvonne Freund-Levi; Lutz Frölich; Rik Vandenberghe; Sarah Westwood; Valerija Dobricic; Frederik Barkhof; Cristina Legido-Quigley; Lars Bertram; Simon Lovestone; Johannes Streffer; Ulf Andreasson; Kaj Blennow; Henrik Zetterberg; Pieter Jelle Visser

doi:10.1016/j.jalz.2019.01.004

Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum

Isabelle Bos, Stephanie Vos, Frans Verhey, Philip Scheltens, Charlotte Teunissen, Sebastiaan Engelborghs, Kristel Sleegers, Giovanni Frisoni, Olivier Blin, Jill C Richardson, Régis Bordet, Magda Tsolaki, Julius Popp, Gwendoline Peyratout, Pablo Martinez-Lage, Mikel Tainta, Alberto Lleó, Peter Johannsen, Yvonne Freund-Levi, Lutz FrölichRik Vandenberghe, Sarah Westwood, Valerija Dobricic, Frederik Barkhof, Cristina Legido-Quigley, Lars Bertram, Simon Lovestone, Johannes Streffer, Ulf Andreasson, Kaj Blennow, Henrik Zetterberg, Pieter Jelle Visser

Research output: Contribution to journal › Article › peer-review

87 Citations (Scopus)

Abstract

INTRODUCTION: We investigated relations between amyloid-β (Aβ) status, apolipoprotein E (APOE) ε4, and cognition, with cerebrospinal fluid markers of neurogranin (Ng), neurofilament light (NFL), YKL-40, and total tau (T-tau).

METHODS: We included 770 individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD)-type dementia from the EMIF-AD Multimodal Biomarker Discovery study. We tested the association of Ng, NFL, YKL-40, and T-tau with Aβ status (Aβ- vs. Aβ+), clinical diagnosis APOE ε4 carriership, baseline cognition, and change in cognition.

RESULTS: Ng and T-tau distinguished between Aβ+ from Aβ- individuals in each clinical group, whereas NFL and YKL-40 were associated with Aβ+ in nondemented individuals only. APOE ε4 carriership did not influence NFL, Ng, and YKL-40 in Aβ+ individuals. NFL was the best predictor of cognitive decline in Aβ+ individuals across the cognitive spectrum.

DISCUSSION: Axonal degeneration, synaptic dysfunction, astroglial activation, and altered tau metabolism are involved already in preclinical AD. NFL may be a useful prognostic marker.

Original language	English
Pages (from-to)	644-654
Number of pages	11
Journal	Alzheimer's & Dementia
Volume	15
Issue number	5
Early online date	2019
DOIs	https://doi.org/10.1016/j.jalz.2019.01.004
Publication status	Published - May 2019

Bibliographical note

Keywords

APOE
Alzheimer's disease
Amyloid-β
Cerebrospinal fluid
Cognition
Neurofilament light
Neurogranin
YKL-40

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Bos, I., Vos, S., Verhey, F., Scheltens, P., Teunissen, C., Engelborghs, S., Sleegers, K., Frisoni, G., Blin, O., Richardson, J. C., Bordet, R., Tsolaki, M., Popp, J., Peyratout, G., Martinez-Lage, P., Tainta, M., Lleó, A., Johannsen, P., Freund-Levi, Y., ... Visser, P. J. (2019). Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum. Alzheimer's & Dementia, 15(5), 644-654. https://doi.org/10.1016/j.jalz.2019.01.004

Bos, Isabelle ; Vos, Stephanie ; Verhey, Frans ; Scheltens, Philip ; Teunissen, Charlotte ; Engelborghs, Sebastiaan ; Sleegers, Kristel ; Frisoni, Giovanni ; Blin, Olivier ; Richardson, Jill C ; Bordet, Régis ; Tsolaki, Magda ; Popp, Julius ; Peyratout, Gwendoline ; Martinez-Lage, Pablo ; Tainta, Mikel ; Lleó, Alberto ; Johannsen, Peter ; Freund-Levi, Yvonne ; Frölich, Lutz ; Vandenberghe, Rik ; Westwood, Sarah ; Dobricic, Valerija ; Barkhof, Frederik ; Legido-Quigley, Cristina ; Bertram, Lars ; Lovestone, Simon ; Streffer, Johannes ; Andreasson, Ulf ; Blennow, Kaj ; Zetterberg, Henrik ; Visser, Pieter Jelle. / Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum. In: Alzheimer's & Dementia. 2019 ; Vol. 15, No. 5. pp. 644-654.

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title = "Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum",

abstract = "INTRODUCTION: We investigated relations between amyloid-β (Aβ) status, apolipoprotein E (APOE) ε4, and cognition, with cerebrospinal fluid markers of neurogranin (Ng), neurofilament light (NFL), YKL-40, and total tau (T-tau).METHODS: We included 770 individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD)-type dementia from the EMIF-AD Multimodal Biomarker Discovery study. We tested the association of Ng, NFL, YKL-40, and T-tau with Aβ status (Aβ- vs. Aβ+), clinical diagnosis APOE ε4 carriership, baseline cognition, and change in cognition.RESULTS: Ng and T-tau distinguished between Aβ+ from Aβ- individuals in each clinical group, whereas NFL and YKL-40 were associated with Aβ+ in nondemented individuals only. APOE ε4 carriership did not influence NFL, Ng, and YKL-40 in Aβ+ individuals. NFL was the best predictor of cognitive decline in Aβ+ individuals across the cognitive spectrum.DISCUSSION: Axonal degeneration, synaptic dysfunction, astroglial activation, and altered tau metabolism are involved already in preclinical AD. NFL may be a useful prognostic marker.",

keywords = "APOE, Alzheimer's disease, Amyloid-β, Cerebrospinal fluid, Cognition, Neurofilament light, Neurogranin, YKL-40",

author = "Isabelle Bos and Stephanie Vos and Frans Verhey and Philip Scheltens and Charlotte Teunissen and Sebastiaan Engelborghs and Kristel Sleegers and Giovanni Frisoni and Olivier Blin and Richardson, {Jill C} and R{\'e}gis Bordet and Magda Tsolaki and Julius Popp and Gwendoline Peyratout and Pablo Martinez-Lage and Mikel Tainta and Alberto Lle{\'o} and Peter Johannsen and Yvonne Freund-Levi and Lutz Fr{\"o}lich and Rik Vandenberghe and Sarah Westwood and Valerija Dobricic and Frederik Barkhof and Cristina Legido-Quigley and Lars Bertram and Simon Lovestone and Johannes Streffer and Ulf Andreasson and Kaj Blennow and Henrik Zetterberg and Visser, {Pieter Jelle}",

year = "2019",

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doi = "10.1016/j.jalz.2019.01.004",

language = "English",

volume = "15",

pages = "644--654",

journal = "Alzheimer's & Dementia",

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publisher = "Elsevier",

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Bos, I, Vos, S, Verhey, F, Scheltens, P, Teunissen, C, Engelborghs, S, Sleegers, K, Frisoni, G, Blin, O, Richardson, JC, Bordet, R, Tsolaki, M, Popp, J, Peyratout, G, Martinez-Lage, P, Tainta, M, Lleó, A, Johannsen, P, Freund-Levi, Y, Frölich, L, Vandenberghe, R, Westwood, S, Dobricic, V, Barkhof, F, Legido-Quigley, C, Bertram, L, Lovestone, S, Streffer, J, Andreasson, U, Blennow, K, Zetterberg, H & Visser, PJ 2019, 'Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum', Alzheimer's & Dementia, vol. 15, no. 5, pp. 644-654. https://doi.org/10.1016/j.jalz.2019.01.004

Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum. / Bos, Isabelle; Vos, Stephanie; Verhey, Frans; Scheltens, Philip; Teunissen, Charlotte; Engelborghs, Sebastiaan; Sleegers, Kristel; Frisoni, Giovanni; Blin, Olivier; Richardson, Jill C; Bordet, Régis; Tsolaki, Magda; Popp, Julius; Peyratout, Gwendoline; Martinez-Lage, Pablo; Tainta, Mikel; Lleó, Alberto; Johannsen, Peter; Freund-Levi, Yvonne; Frölich, Lutz; Vandenberghe, Rik; Westwood, Sarah; Dobricic, Valerija; Barkhof, Frederik; Legido-Quigley, Cristina; Bertram, Lars; Lovestone, Simon; Streffer, Johannes; Andreasson, Ulf; Blennow, Kaj; Zetterberg, Henrik; Visser, Pieter Jelle.

In: Alzheimer's & Dementia, Vol. 15, No. 5, 05.2019, p. 644-654.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum

AU - Bos, Isabelle

AU - Vos, Stephanie

AU - Verhey, Frans

AU - Scheltens, Philip

AU - Teunissen, Charlotte

AU - Engelborghs, Sebastiaan

AU - Sleegers, Kristel

AU - Frisoni, Giovanni

AU - Blin, Olivier

AU - Richardson, Jill C

AU - Bordet, Régis

AU - Tsolaki, Magda

AU - Popp, Julius

AU - Peyratout, Gwendoline

AU - Martinez-Lage, Pablo

AU - Tainta, Mikel

AU - Lleó, Alberto

AU - Johannsen, Peter

AU - Freund-Levi, Yvonne

AU - Frölich, Lutz

AU - Vandenberghe, Rik

AU - Westwood, Sarah

AU - Dobricic, Valerija

AU - Barkhof, Frederik

AU - Legido-Quigley, Cristina

AU - Bertram, Lars

AU - Lovestone, Simon

AU - Streffer, Johannes

AU - Andreasson, Ulf

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Visser, Pieter Jelle

PY - 2019/5

Y1 - 2019/5

N2 - INTRODUCTION: We investigated relations between amyloid-β (Aβ) status, apolipoprotein E (APOE) ε4, and cognition, with cerebrospinal fluid markers of neurogranin (Ng), neurofilament light (NFL), YKL-40, and total tau (T-tau).METHODS: We included 770 individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD)-type dementia from the EMIF-AD Multimodal Biomarker Discovery study. We tested the association of Ng, NFL, YKL-40, and T-tau with Aβ status (Aβ- vs. Aβ+), clinical diagnosis APOE ε4 carriership, baseline cognition, and change in cognition.RESULTS: Ng and T-tau distinguished between Aβ+ from Aβ- individuals in each clinical group, whereas NFL and YKL-40 were associated with Aβ+ in nondemented individuals only. APOE ε4 carriership did not influence NFL, Ng, and YKL-40 in Aβ+ individuals. NFL was the best predictor of cognitive decline in Aβ+ individuals across the cognitive spectrum.DISCUSSION: Axonal degeneration, synaptic dysfunction, astroglial activation, and altered tau metabolism are involved already in preclinical AD. NFL may be a useful prognostic marker.

AB - INTRODUCTION: We investigated relations between amyloid-β (Aβ) status, apolipoprotein E (APOE) ε4, and cognition, with cerebrospinal fluid markers of neurogranin (Ng), neurofilament light (NFL), YKL-40, and total tau (T-tau).METHODS: We included 770 individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD)-type dementia from the EMIF-AD Multimodal Biomarker Discovery study. We tested the association of Ng, NFL, YKL-40, and T-tau with Aβ status (Aβ- vs. Aβ+), clinical diagnosis APOE ε4 carriership, baseline cognition, and change in cognition.RESULTS: Ng and T-tau distinguished between Aβ+ from Aβ- individuals in each clinical group, whereas NFL and YKL-40 were associated with Aβ+ in nondemented individuals only. APOE ε4 carriership did not influence NFL, Ng, and YKL-40 in Aβ+ individuals. NFL was the best predictor of cognitive decline in Aβ+ individuals across the cognitive spectrum.DISCUSSION: Axonal degeneration, synaptic dysfunction, astroglial activation, and altered tau metabolism are involved already in preclinical AD. NFL may be a useful prognostic marker.

KW - APOE

KW - Alzheimer's disease

KW - Amyloid-β

KW - Cerebrospinal fluid

KW - Cognition

KW - Neurofilament light

KW - Neurogranin

KW - YKL-40

UR - http://www.scopus.com/inward/record.url?scp=85062454355&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2019.01.004

DO - 10.1016/j.jalz.2019.01.004

M3 - Article

C2 - 30853464

VL - 15

SP - 644

EP - 654

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

SN - 1552-5260

IS - 5

ER -

Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum

Abstract

Bibliographical note

Keywords

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