TY  - JOUR
AU  - Teipel, Stefan
AU  - Dyrba, Martin
AU  - Ballarini, Tommaso
AU  - Brosseron, Frederic
AU  - Bruno, Davide
AU  - Bürger, Katharina
AU  - Cosma, Nicoleta-Carmen
AU  - Dechent, Peter
AU  - Dobisch, Laura
AU  - Düzel, Emrah
AU  - Ewers, Michael
AU  - Fliessbach, Klaus
AU  - Haynes, John D
AU  - Janowitz, Daniel
AU  - Kilimann, Ingo
AU  - Laske, Christoph
AU  - Maier, Franziska
AU  - Metzger, Coraline D
AU  - Munk, Matthias H
AU  - Peters, Oliver
AU  - Pomara, Nunzio
AU  - Preis, Lukas
AU  - Priller, Josef
AU  - Ramírez, Alfredo
AU  - Roy, Nina
AU  - Scheffler, Klaus
AU  - Schneider, Anja
AU  - Schott, Björn H
AU  - Spottke, Annika
AU  - Spruth, Eike J
AU  - Wagner, Michael
AU  - Wiltfang, Jens
AU  - Jessen, Frank
AU  - Heneka, Michael T
TI  - Association of Cholinergic Basal Forebrain Volume and Functional Connectivity with Markers of Inflammatory Response in the Alzheimer's Disease Spectrum.
JO  - Journal of Alzheimer's disease
VL  - 85
IS  - 3
SN  - 1875-8908
CY  - Amsterdam
PB  - IOS Press
M1  - DZNE-2022-00263
SP  - 1267 - 1282
PY  - 2022
AB  - 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.To study the association of cholinergic basal forebrain volume and functional connectivity with measures of neuroinflammation in people from the AD spectrum.We studied 261 cases from the DELCODE cohort, 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.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 Aβ42/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.Our data-driven analyses generate the hypothesis that cholinergic basal forebrain may be involved in the neuroinflammation response to Aβ42 and phospho-tau pathology in people from the AD spectrum. This hypothesis needs to be tested in independent samples.
KW  - Aged
KW  - Alzheimer Disease: pathology
KW  - Basal Forebrain: pathology
KW  - Biomarkers: blood
KW  - Biomarkers: cerebrospinal fluid
KW  - Cholinergic Agents
KW  - Cognitive Dysfunction: pathology
KW  - Cohort Studies
KW  - Female
KW  - Humans
KW  - Inflammation: pathology
KW  - Magnetic Resonance Imaging
KW  - Male
KW  - Alzheimer’s disease (Other)
KW  - MRI (Other)
KW  - cerebrospinal fluid (Other)
KW  - cholinergic system (Other)
KW  - neuroinflammation (Other)
KW  - plasma (Other)
KW  - sTREM2 (Other)
KW  - Biomarkers (NLM Chemicals)
KW  - Cholinergic Agents (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:34924387
DO  - DOI:10.3233/JAD-215196
UR  - https://pub.dzne.de/record/163503
ER  -