Teipel, Stefan J., Dyrba, Martin ORCID: 0000-0002-3353-3167, Ballarini, Tommaso, Brosseron, Frederic, Bruno, Davide ORCID: 0000-0003-1943-9905, Buerger, Katharina, Cosma, Nicoleta-Carmen, Dechent, Peter, Dobisch, Laura, Duezel, Emrah, Ewers, Michael, Fliessbach, Klaus, Haynes, John D., Janowitz, Daniel, Kilimann, Ingo, Laske, Christoph, Maier, Franziska ORCID: 0000-0002-9335-9594, Metzger, Coraline D., Munk, Matthias H., Peters, Oliver ORCID: 0000-0003-0568-2998, Pomara, Nunzio, Preis, Lukas ORCID: 0000-0001-7601-6410, Priller, Josef, Ramirez, Alfredo ORCID: 0000-0003-4991-763X, Roy, Nina, Scheffler, Klaus, Schneider, Anja ORCID: 0000-0001-9540-8700, Schott, Bjoern H., Spottke, Annika, Spruth, Eike J., Wagner, Michael ORCID: 0000-0003-2589-6440, Wiltfang, Jens, Jessen, Frank and Heneka, Michael T. (2022). Association of Cholinergic Basal Forebrain Volume and Functional Connectivity with Markers of Inflammatory Response in the Alzheimer's Disease Spectrum. J. Alzheimers Dis., 85 (3). S. 1267 - 1283. AMSTERDAM: IOS PRESS. ISSN 1875-8908

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Abstract

Background: Inflammation has been described as a key pathogenic event in Alzheimer's disease (AD), downstream of amyloid and tau pathology. Preclinical and clinical data suggest that the cholinergic basal forebrain may moderate inflammatory response to different pathologies. Objective: To study the association of cholinergic basal forebrain volume and functional connectivity with measures of neuroinflammation in people from the AD spectrum. Methods: We studied 261 cases from the DELCODEcohort, including people with subjective cognitive decline, mild cognitive impairment, AD dementia, first degree relatives, and healthy controls. Using Bayesian ANCOVA, we tested associations of MRI indices of cholinergic basal forebrain volume and functional connectivity with cerebrospinal fluid (CSF) levels of sTREM2 as a marker of microglia activation, and serum levels of complement C3. Using Bayesian elastic net regression, we determined associations between basal forebrain measures and a large inflammation marker panel from CSF and serum. Results: We found anecdotal to moderate evidence in favor of the absence of an effect of basal forebrain volume and functional connectivity on CSF sTREM2 and serum C3 levels both in A beta(42)/ptau-positive and negative cases. Bayesian elastic net regression identified several CSF and serum markers of inflammation that were associated with basal forebrain volume and functional connectivity. The effect sizes were moderate to small. Conclusion: Our data-driven analyses generate the hypothesis that cholinergic basal forebrain may be involved in the neuroinflammation response to A beta(42) and phospho-tau pathology in people from the AD spectrum. This hypothesis needs to be tested in independent samples.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Teipel, Stefan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dyrba, MartinUNSPECIFIEDorcid.org/0000-0002-3353-3167UNSPECIFIED
Ballarini, TommasoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brosseron, FredericUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruno, DavideUNSPECIFIEDorcid.org/0000-0003-1943-9905UNSPECIFIED
Buerger, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cosma, Nicoleta-CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dechent, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dobisch, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duezel, EmrahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ewers, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fliessbach, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haynes, John D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janowitz, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kilimann, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laske, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maier, FranziskaUNSPECIFIEDorcid.org/0000-0002-9335-9594UNSPECIFIED
Metzger, Coraline D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Munk, Matthias H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peters, OliverUNSPECIFIEDorcid.org/0000-0003-0568-2998UNSPECIFIED
Pomara, NunzioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Preis, LukasUNSPECIFIEDorcid.org/0000-0001-7601-6410UNSPECIFIED
Priller, JosefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramirez, AlfredoUNSPECIFIEDorcid.org/0000-0003-4991-763XUNSPECIFIED
Roy, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheffler, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, AnjaUNSPECIFIEDorcid.org/0000-0001-9540-8700UNSPECIFIED
Schott, Bjoern H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spottke, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spruth, Eike J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, MichaelUNSPECIFIEDorcid.org/0000-0003-2589-6440UNSPECIFIED
Wiltfang, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jessen, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heneka, Michael T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-696662
DOI: 10.3233/JAD-215196
Journal or Publication Title: J. Alzheimers Dis.
Volume: 85
Number: 3
Page Range: S. 1267 - 1283
Date: 2022
Publisher: IOS PRESS
Place of Publication: AMSTERDAM
ISSN: 1875-8908
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MILD COGNITIVE IMPAIRMENT; DIAGNOSTIC GUIDELINES; MICROGLIAL ACTIVATION; NATIONAL INSTITUTE; NEUROINFLAMMATION; RECOMMENDATIONS; WORKGROUPS; HYPOTHESIS; BIOMARKERS; SHRINKAGEMultiple languages
NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69666

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