Association of latent factors of neuroinflammation with Alzheimer's disease pathology and longitudinal cognitive decline

Stefan J. Teipel; Martin Dyrba; Luca Kleineidam; Frederic Brosseron; Fedor Levin; Davide Bruno; Katharina Buerger; Nicoleta Cosma; Luisa Sophie Schneider; Emrah Düzel; Wenzel Glanz; Klaus Fliessbach; Daniel Janowitz; Ingo Kilimann; Christoph Laske; Matthias H. Munk; Franziska Maier; Oliver Peters; Nunzio Pomara; Robert Perneczky; Boris Stephan Rauchmann; Josef Priller; Alfredo Ramirez; Nina Roy; Anja Schneider; Annika Spottke; Eike J. Spruth; Sandra Roeske; Michael Wagner; Jens Wiltfang; Steffen Wolfsgruber; Claudia Bartels; Frank Jessen; Michael T. Heneka

doi:10.1002/dad2.12510

Association of latent factors of neuroinflammation with Alzheimer's disease pathology and longitudinal cognitive decline

Stefan J. Teipel, Martin Dyrba, Luca Kleineidam, Frederic Brosseron, Fedor Levin, Davide Bruno, Katharina Buerger, Nicoleta Cosma, Luisa Sophie Schneider, Emrah Düzel, Wenzel Glanz, Klaus Fliessbach, Daniel Janowitz, Ingo Kilimann, Christoph Laske, Matthias H. Munk, Franziska Maier, Oliver Peters, Nunzio Pomara, Robert PerneczkyBoris Stephan Rauchmann, Josef Priller, Alfredo Ramirez, Nina Roy, Anja Schneider, Annika Spottke, Eike J. Spruth, Sandra Roeske, Michael Wagner, Jens Wiltfang, Steffen Wolfsgruber, Claudia Bartels, Frank Jessen, Michael T. Heneka

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Abstract

INTRODUCTION: We investigated the association of inflammatory mechanisms with markers of Alzheimer's disease (AD) pathology and rates of cognitive decline in the AD spectrum. METHODS: We studied 296 cases from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study (DELCODE) cohort, and an extension cohort of 276 cases of the Alzheimer's Disease Neuroimaging Initiative study. Using Bayesian confirmatory factor analysis, we constructed latent factors for synaptic integrity, microglia, cerebrovascular endothelial function, cytokine/chemokine, and complement components of the inflammatory response using a set of inflammatory markers in cerebrospinal fluid. RESULTS: We found strong evidence for an association of synaptic integrity, microglia response, and cerebrovascular endothelial function with a latent factor of AD pathology and with rates of cognitive decline. We found evidence against an association of complement and cytokine/chemokine factors with AD pathology and rates of cognitive decline. DISCUSSION: Latent factors provided access to directly unobservable components of the neuroinflammatory response and their association with AD pathology and cognitive decline.

Originalsprache	Englisch
Aufsatznummer	e12510
Fachzeitschrift	Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Jahrgang	16
Ausgabenummer	1
DOIs	https://doi.org/10.1002/dad2.12510
Publikationsstatus	Veröffentlicht - 1 Jan. 2024

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Teipel, S. J., Dyrba, M., Kleineidam, L., Brosseron, F., Levin, F., Bruno, D., Buerger, K., Cosma, N., Schneider, L. S., Düzel, E., Glanz, W., Fliessbach, K., Janowitz, D., Kilimann, I., Laske, C., Munk, M. H., Maier, F., Peters, O., Pomara, N., ... Heneka, M. T. (2024). Association of latent factors of neuroinflammation with Alzheimer's disease pathology and longitudinal cognitive decline. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 16(1), Artikel e12510. https://doi.org/10.1002/dad2.12510

@article{0cc3119ef8dd4d4ca5205522d52b7add,

title = "Association of latent factors of neuroinflammation with Alzheimer's disease pathology and longitudinal cognitive decline",

abstract = "INTRODUCTION: We investigated the association of inflammatory mechanisms with markers of Alzheimer's disease (AD) pathology and rates of cognitive decline in the AD spectrum. METHODS: We studied 296 cases from the Deutsches Zentrum f{\"u}r Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study (DELCODE) cohort, and an extension cohort of 276 cases of the Alzheimer's Disease Neuroimaging Initiative study. Using Bayesian confirmatory factor analysis, we constructed latent factors for synaptic integrity, microglia, cerebrovascular endothelial function, cytokine/chemokine, and complement components of the inflammatory response using a set of inflammatory markers in cerebrospinal fluid. RESULTS: We found strong evidence for an association of synaptic integrity, microglia response, and cerebrovascular endothelial function with a latent factor of AD pathology and with rates of cognitive decline. We found evidence against an association of complement and cytokine/chemokine factors with AD pathology and rates of cognitive decline. DISCUSSION: Latent factors provided access to directly unobservable components of the neuroinflammatory response and their association with AD pathology and cognitive decline.",

keywords = "amyloid, chemokine factors, complement, endothelial function, microglia, structural equation models, tau",

author = "Teipel, {Stefan J.} and Martin Dyrba and Luca Kleineidam and Frederic Brosseron and Fedor Levin and Davide Bruno and Katharina Buerger and Nicoleta Cosma and Schneider, {Luisa Sophie} and Emrah D{\"u}zel and Wenzel Glanz and Klaus Fliessbach and Daniel Janowitz and Ingo Kilimann and Christoph Laske and Munk, {Matthias H.} and Franziska Maier and Oliver Peters and Nunzio Pomara and Robert Perneczky and Rauchmann, {Boris Stephan} and Josef Priller and Alfredo Ramirez and Nina Roy and Anja Schneider and Annika Spottke and Spruth, {Eike J.} and Sandra Roeske and Michael Wagner and Jens Wiltfang and Steffen Wolfsgruber and Claudia Bartels and Frank Jessen and Heneka, {Michael T.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2024",

month = jan,

day = "1",

doi = "10.1002/dad2.12510",

language = "English",

volume = "16",

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

issn = "2352-8729",

publisher = "John Wiley and Sons Inc.",

number = "1",

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Teipel, SJ, Dyrba, M, Kleineidam, L, Brosseron, F, Levin, F, Bruno, D, Buerger, K, Cosma, N, Schneider, LS, Düzel, E, Glanz, W, Fliessbach, K, Janowitz, D, Kilimann, I, Laske, C, Munk, MH, Maier, F, Peters, O, Pomara, N, Perneczky, R, Rauchmann, BS, Priller, J, Ramirez, A, Roy, N, Schneider, A, Spottke, A, Spruth, EJ, Roeske, S, Wagner, M, Wiltfang, J, Wolfsgruber, S, Bartels, C, Jessen, F & Heneka, MT 2024, 'Association of latent factors of neuroinflammation with Alzheimer's disease pathology and longitudinal cognitive decline', Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, Jg. 16, Nr. 1, e12510. https://doi.org/10.1002/dad2.12510

TY - JOUR

T1 - Association of latent factors of neuroinflammation with Alzheimer's disease pathology and longitudinal cognitive decline

AU - Teipel, Stefan J.

AU - Dyrba, Martin

AU - Kleineidam, Luca

AU - Brosseron, Frederic

AU - Levin, Fedor

AU - Bruno, Davide

AU - Buerger, Katharina

AU - Cosma, Nicoleta

AU - Schneider, Luisa Sophie

AU - Düzel, Emrah

AU - Glanz, Wenzel

AU - Fliessbach, Klaus

AU - Janowitz, Daniel

AU - Kilimann, Ingo

AU - Laske, Christoph

AU - Munk, Matthias H.

AU - Maier, Franziska

AU - Peters, Oliver

AU - Pomara, Nunzio

AU - Perneczky, Robert

AU - Rauchmann, Boris Stephan

AU - Priller, Josef

AU - Ramirez, Alfredo

AU - Roy, Nina

AU - Schneider, Anja

AU - Spottke, Annika

AU - Spruth, Eike J.

AU - Roeske, Sandra

AU - Wagner, Michael

AU - Wiltfang, Jens

AU - Wolfsgruber, Steffen

AU - Bartels, Claudia

AU - Jessen, Frank

AU - Heneka, Michael T.

PY - 2024/1/1

Y1 - 2024/1/1

N2 - INTRODUCTION: We investigated the association of inflammatory mechanisms with markers of Alzheimer's disease (AD) pathology and rates of cognitive decline in the AD spectrum. METHODS: We studied 296 cases from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study (DELCODE) cohort, and an extension cohort of 276 cases of the Alzheimer's Disease Neuroimaging Initiative study. Using Bayesian confirmatory factor analysis, we constructed latent factors for synaptic integrity, microglia, cerebrovascular endothelial function, cytokine/chemokine, and complement components of the inflammatory response using a set of inflammatory markers in cerebrospinal fluid. RESULTS: We found strong evidence for an association of synaptic integrity, microglia response, and cerebrovascular endothelial function with a latent factor of AD pathology and with rates of cognitive decline. We found evidence against an association of complement and cytokine/chemokine factors with AD pathology and rates of cognitive decline. DISCUSSION: Latent factors provided access to directly unobservable components of the neuroinflammatory response and their association with AD pathology and cognitive decline.

AB - INTRODUCTION: We investigated the association of inflammatory mechanisms with markers of Alzheimer's disease (AD) pathology and rates of cognitive decline in the AD spectrum. METHODS: We studied 296 cases from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study (DELCODE) cohort, and an extension cohort of 276 cases of the Alzheimer's Disease Neuroimaging Initiative study. Using Bayesian confirmatory factor analysis, we constructed latent factors for synaptic integrity, microglia, cerebrovascular endothelial function, cytokine/chemokine, and complement components of the inflammatory response using a set of inflammatory markers in cerebrospinal fluid. RESULTS: We found strong evidence for an association of synaptic integrity, microglia response, and cerebrovascular endothelial function with a latent factor of AD pathology and with rates of cognitive decline. We found evidence against an association of complement and cytokine/chemokine factors with AD pathology and rates of cognitive decline. DISCUSSION: Latent factors provided access to directly unobservable components of the neuroinflammatory response and their association with AD pathology and cognitive decline.

KW - amyloid

KW - chemokine factors

KW - complement

KW - endothelial function

KW - microglia

KW - structural equation models

KW - tau

UR - http://www.scopus.com/inward/record.url?scp=85181927034&partnerID=8YFLogxK

U2 - 10.1002/dad2.12510

DO - 10.1002/dad2.12510

M3 - Article

AN - SCOPUS:85181927034

SN - 2352-8729

VL - 16

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

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

IS - 1

M1 - e12510

ER -

Association of latent factors of neuroinflammation with Alzheimer's disease pathology and longitudinal cognitive decline

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