Association of Cholinergic Basal Forebrain Volume and Functional Connectivity with Markers of Inflammatory Response in the Alzheimer's Disease Spectrum

Teipel, Stefan J.; Dyrba, Martin; Ballarini, Tommaso; Brosseron, Frederic; Bruno, Davide; 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; Metzger, Coraline D.; Munk, Matthias H.; Peters, Oliver; Pomara, Nunzio; Preis, Lukas; Priller, Josef; Ramirez, Alfredo; Roy, Nina; Scheffler, Klaus; Schneider, Anja; Schott, Bjoern H.; Spottke, Annika; Spruth, Eike J.; Wagner, Michael; Wiltfang, Jens; Jessen, Frank und Heneka, Michael T. (2022): Association of Cholinergic Basal Forebrain Volume and Functional Connectivity with Markers of Inflammatory Response in the Alzheimer's Disease Spectrum. In: Journal of Alzheimers Disease, Bd. 85, Nr. 3: S. 1267-1282

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1387-2877
• Sprache: Englisch