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, R. gis Bordet, Magda Tsolaki, Julius Popp, Gwendoline Peyratout, Pablo Martinez-Lage, Mikel Tainta, Alberto Lleó, Peter Johannsen, Yvonne Freund-Levi, Lutz Frölich & 12 others 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

Research output: Contribution to journalArticleAcademicpeer-review

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.
LanguageEnglish
JournalAlzheimer's and Dementia
DOIs
Publication statusPublished - 2019

Cite this

Bos, Isabelle ; Vos, Stephanie ; Verhey, Frans ; Scheltens, Philip ; Teunissen, Charlotte ; Engelborghs, Sebastiaan ; Sleegers, Kristel ; Frisoni, Giovanni ; Blin, Olivier ; Richardson, Jill C. ; Bordet, R. gis ; 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 and Dementia. 2019.
@article{99b4b404cd1f42a78b19e0a5dc14580a,
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.",
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 Bordet, {R. gis} 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",
doi = "10.1016/j.jalz.2019.01.004",
language = "English",
journal = "Alzheimers & Dementia",
issn = "1552-5260",
publisher = "Elsevier",

}

Bos, I, Vos, S, Verhey, F, Scheltens, P, Teunissen, C, Engelborghs, S, Sleegers, K, Frisoni, G, Blin, O, Richardson, JC, Bordet, RG, 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 and Dementia. 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, R. gis; 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 and Dementia, 2019.

Research output: Contribution to journalArticleAcademicpeer-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, R. gis

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

Y1 - 2019

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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85062454355&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30853464

U2 - 10.1016/j.jalz.2019.01.004

DO - 10.1016/j.jalz.2019.01.004

M3 - Article

JO - Alzheimers & Dementia

T2 - Alzheimers & Dementia

JF - Alzheimers & Dementia

SN - 1552-5260

ER -