Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and...

Paper

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.

Analysis

Paper intelligence

Summary

This study examined cerebrospinal fluid (CSF) biomarkers (neurogranin, neurofilament light, YKL-40, and total tau) in relation to amyloid-beta status, APOE ε4, and cognition across the Alzheimer's disease spectrum, finding that Ng and T-tau differentiate amyloid status, while NFL predicts cognitive decline.

Key findings

Ng and T-tau distinguished Aβ+ from Aβ- individuals in all clinical groups.
NFL and YKL-40 were associated with Aβ+ status only in non-demented individuals.
APOE ε4 carriership did not affect NFL, Ng, and YKL-40 in Aβ+ individuals.
NFL was the strongest predictor of cognitive decline in Aβ+ individuals across the spectrum.

Methods

Investigated relations between Aβ status, APOE ε4, and cognition with CSF markers Ng, NFL, YKL-40, and T-tau.
Included 770 individuals with normal cognition, mild cognitive impairment, and AD-type dementia.
Tested associations of CSF markers with Aβ status, clinical diagnosis, APOE ε4 carriership, baseline cognition, and cognitive change.

Limitations

The study included individuals from a specific cohort (EMIF-AD Multimodal Biomarker Discovery study).
The associations of NFL and YKL-40 with Aβ+ status were limited to non-demented individuals.
The influence of APOE ε4 was specifically examined in Aβ+ individuals.

Applications

Potential for early diagnosis of AD.
Prognostic marker for cognitive decline in AD.
Understanding pathological mechanisms in preclinical AD.

Confidence95%

Discovery

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Source record

Publication metadata

Authors: Isabelle Bos; Stephanie J. B. Vos; Frans Verhey; Philip Scheltens; Charlotte E. Teunissen; Sebastiaan Engelborghs; Kristel Sleegers; Giovanni B. Frisoni; Olivier Blin; Jill Richardson; Régis Bordet; Magda Tsolaki; Julius Popp; Gwendoline Peyratout; Pablo Martínez‐Lage; Mikel Tainta; Alberto Lleó; Peter Johannsen; Yvonne Freund‐Levi; Lutz Frölich; Rik Vandenberghe; Sarah Westwood; Valerija Dobričić; Frederik Barkhof; Cristina Legido‐Quigley; Lars Bertram; Simon Lovestone; Johannes Streffer; Ulf Andréasson; Kaj Blennow; Henrik Zetterberg; Pieter Jelle Visser
Published: Mar 7, 2019
Journal or venue: Alzheimer s & Dementia
DOI: 10.1016/j.jalz.2019.01.004
Paper type: journal article
Source: Openalex

DOI OpenAlex