CSF proteomic signature predicts progression to Alzheimer's disease dementia

Eleonora M Vromen; Marta Del Campo Milán; Philip Scheltens; Charlotte E Teunissen; Pieter Jelle Visser; Betty M Tijms

doi:10.1002/trc2.12240

CSF proteomic signature predicts progression to Alzheimer's disease dementia

Eleonora M Vromen^*, Marta Del Campo Milán, Philip Scheltens, Charlotte E Teunissen, Pieter Jelle Visser, Betty M Tijms

^*Corresponding author for this work

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

Abstract

Introduction: Individuals in the Alzheimer's disease (AD) continuum with mild cognitive impairment (prodromal AD) are at increased risk to develop dementia. Still, underlying pathophysiological processes remain unclear. We studied whether cerebrospinal fluid (CSF) proteome changes are related to time to clinical progression in prodromal AD.

Methods: We measured 671 CSF proteins in 49 prodromal AD individuals (67±7 years old, 22 [45%] female) from the Amsterdam Dementia Cohort. Associations of protein levels with time to dementia onset were tested with Cox regression models, followed by biological pathway enrichment analysis.

Results: Eighteen (36%) individuals developed dementia during follow-up. In total, 128 (98%) proteins were associated with a 1.4- to 17-fold increased risk of progression to dementia (all P < .05). These proteins showed enrichment for immune system processes, signal transduction, neuronal death, and neurodevelopmental biology.

Discussion: CSF proteome changes related to rate of progression to dementia can be detected in prodromal AD, providing more insight into processes involved in early AD pathophysiology.

Original language	English
Article number	e12240
Number of pages	5
Journal	Alzheimer's and Dementia: Translational Research and Clinical Interventions
Volume	8
Issue number	1
DOIs	https://doi.org/10.1002/trc2.12240
Publication status	Published - 2022

Keywords

ASSOCIATION WORKGROUPS
Alzheimer's disease
CEREBROSPINAL-FLUID BIOMARKERS
DIAGNOSTIC GUIDELINES
MILD COGNITIVE IMPAIRMENT
NATIONAL INSTITUTE
RECOMMENDATIONS
cerebrospinal fluid
mild cognitive impairment
prognosis
proteomics

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@article{9cf2f0fc016649d69b464c064fb64dce,

title = "CSF proteomic signature predicts progression to Alzheimer's disease dementia",

abstract = "Introduction: Individuals in the Alzheimer's disease (AD) continuum with mild cognitive impairment (prodromal AD) are at increased risk to develop dementia. Still, underlying pathophysiological processes remain unclear. We studied whether cerebrospinal fluid (CSF) proteome changes are related to time to clinical progression in prodromal AD.Methods: We measured 671 CSF proteins in 49 prodromal AD individuals (67±7 years old, 22 [45%] female) from the Amsterdam Dementia Cohort. Associations of protein levels with time to dementia onset were tested with Cox regression models, followed by biological pathway enrichment analysis.Results: Eighteen (36%) individuals developed dementia during follow-up. In total, 128 (98%) proteins were associated with a 1.4- to 17-fold increased risk of progression to dementia (all P < .05). These proteins showed enrichment for immune system processes, signal transduction, neuronal death, and neurodevelopmental biology.Discussion: CSF proteome changes related to rate of progression to dementia can be detected in prodromal AD, providing more insight into processes involved in early AD pathophysiology.",

keywords = "ASSOCIATION WORKGROUPS, Alzheimer's disease, CEREBROSPINAL-FLUID BIOMARKERS, DIAGNOSTIC GUIDELINES, MILD COGNITIVE IMPAIRMENT, NATIONAL INSTITUTE, RECOMMENDATIONS, cerebrospinal fluid, mild cognitive impairment, prognosis, proteomics",

author = "Vromen, {Eleonora M} and {Del Campo Mil{\'a}n}, Marta and Philip Scheltens and Teunissen, {Charlotte E} and Visser, {Pieter Jelle} and Tijms, {Betty M}",

note = "{\textcopyright} 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.",

year = "2022",

doi = "10.1002/trc2.12240",

language = "English",

volume = "8",

journal = "Alzheimer's and Dementia: Translational Research and Clinical Interventions",

issn = "2352-8737",

publisher = "Elsevier Inc.",

number = "1",

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T1 - CSF proteomic signature predicts progression to Alzheimer's disease dementia

AU - Vromen, Eleonora M

AU - Del Campo Milán, Marta

AU - Scheltens, Philip

AU - Teunissen, Charlotte E

AU - Visser, Pieter Jelle

AU - Tijms, Betty M

PY - 2022

Y1 - 2022

N2 - Introduction: Individuals in the Alzheimer's disease (AD) continuum with mild cognitive impairment (prodromal AD) are at increased risk to develop dementia. Still, underlying pathophysiological processes remain unclear. We studied whether cerebrospinal fluid (CSF) proteome changes are related to time to clinical progression in prodromal AD.Methods: We measured 671 CSF proteins in 49 prodromal AD individuals (67±7 years old, 22 [45%] female) from the Amsterdam Dementia Cohort. Associations of protein levels with time to dementia onset were tested with Cox regression models, followed by biological pathway enrichment analysis.Results: Eighteen (36%) individuals developed dementia during follow-up. In total, 128 (98%) proteins were associated with a 1.4- to 17-fold increased risk of progression to dementia (all P < .05). These proteins showed enrichment for immune system processes, signal transduction, neuronal death, and neurodevelopmental biology.Discussion: CSF proteome changes related to rate of progression to dementia can be detected in prodromal AD, providing more insight into processes involved in early AD pathophysiology.

AB - Introduction: Individuals in the Alzheimer's disease (AD) continuum with mild cognitive impairment (prodromal AD) are at increased risk to develop dementia. Still, underlying pathophysiological processes remain unclear. We studied whether cerebrospinal fluid (CSF) proteome changes are related to time to clinical progression in prodromal AD.Methods: We measured 671 CSF proteins in 49 prodromal AD individuals (67±7 years old, 22 [45%] female) from the Amsterdam Dementia Cohort. Associations of protein levels with time to dementia onset were tested with Cox regression models, followed by biological pathway enrichment analysis.Results: Eighteen (36%) individuals developed dementia during follow-up. In total, 128 (98%) proteins were associated with a 1.4- to 17-fold increased risk of progression to dementia (all P < .05). These proteins showed enrichment for immune system processes, signal transduction, neuronal death, and neurodevelopmental biology.Discussion: CSF proteome changes related to rate of progression to dementia can be detected in prodromal AD, providing more insight into processes involved in early AD pathophysiology.

KW - ASSOCIATION WORKGROUPS

KW - Alzheimer's disease

KW - CEREBROSPINAL-FLUID BIOMARKERS

KW - DIAGNOSTIC GUIDELINES

KW - MILD COGNITIVE IMPAIRMENT

KW - NATIONAL INSTITUTE

KW - RECOMMENDATIONS

KW - cerebrospinal fluid

KW - mild cognitive impairment

KW - prognosis

KW - proteomics

U2 - 10.1002/trc2.12240

DO - 10.1002/trc2.12240

M3 - Article

C2 - 35229020

SN - 2352-8737

VL - 8

JO - Alzheimer's and Dementia: Translational Research and Clinical Interventions

JF - Alzheimer's and Dementia: Translational Research and Clinical Interventions

IS - 1

M1 - e12240

ER -

CSF proteomic signature predicts progression to Alzheimer's disease dementia

Abstract

Keywords

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