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@ARTICLE{Teipel:163503,
author = {Teipel, Stefan and Dyrba, Martin and Ballarini, Tommaso and
Brosseron, Frederic and Bruno, Davide and Bürger, Katharina
and Cosma, Nicoleta-Carmen and Dechent, Peter and Dobisch,
Laura and Düzel, Emrah and Ewers, Michael and Fliessbach,
Klaus and Haynes, John D and Janowitz, Daniel and Kilimann,
Ingo and Laske, Christoph and Maier, Franziska and Metzger,
Coraline D and Munk, Matthias H and Peters, Oliver and
Pomara, Nunzio and Preis, Lukas and Priller, Josef and
Ramírez, Alfredo and Roy, Nina and Scheffler, Klaus and
Schneider, Anja and Schott, Björn H and Spottke, Annika and
Spruth, Eike J and Wagner, Michael and Wiltfang, Jens and
Jessen, Frank and Heneka, Michael T},
title = {{A}ssociation of {C}holinergic {B}asal {F}orebrain {V}olume
and {F}unctional {C}onnectivity with {M}arkers of
{I}nflammatory {R}esponse in the {A}lzheimer's {D}isease
{S}pectrum.},
journal = {Journal of Alzheimer's disease},
volume = {85},
number = {3},
issn = {1875-8908},
address = {Amsterdam},
publisher = {IOS Press},
reportid = {DZNE-2022-00263},
pages = {1267 - 1282},
year = {2022},
abstract = {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.},
keywords = {Aged / Alzheimer Disease: pathology / Basal Forebrain:
pathology / Biomarkers: blood / Biomarkers: cerebrospinal
fluid / Cholinergic Agents / Cognitive Dysfunction:
pathology / Cohort Studies / Female / Humans / Inflammation:
pathology / Magnetic Resonance Imaging / Male /
Alzheimer’s disease (Other) / MRI (Other) / cerebrospinal
fluid (Other) / cholinergic system (Other) /
neuroinflammation (Other) / plasma (Other) / sTREM2 (Other)
/ Biomarkers (NLM Chemicals) / Cholinergic Agents (NLM
Chemicals)},
cin = {AG Teipel / AG Wagner / Biomarker / AG Speck / AG Simons /
Patient Studies Bonn / Core ICRU / Magdeburg common / AG
Gasser / AG Endres / AG Priller / Clinical Research Platform
(CRP) / AG Schneider / AG Fischer / AG Klockgether / AG
Wiltfang / AG Jessen / AG Dichgans / AG Düzel / Delcode},
ddc = {610},
cid = {I:(DE-2719)1510100 / I:(DE-2719)1011201 /
I:(DE-2719)1011301 / I:(DE-2719)1340009 / I:(DE-2719)1110008
/ I:(DE-2719)1011101 / I:(DE-2719)1240005 /
I:(DE-2719)6000015 / I:(DE-2719)1210000 / I:(DE-2719)1811005
/ I:(DE-2719)5000007 / I:(DE-2719)1011401 /
I:(DE-2719)1011305 / I:(DE-2719)1410002 / I:(DE-2719)1011001
/ I:(DE-2719)1410006 / I:(DE-2719)1011102 /
I:(DE-2719)5000022 / I:(DE-2719)5000006 /
I:(DE-2719)5000034},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 351 -
Brain Function (POF4-351) / 352 - Disease Mechanisms
(POF4-352)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-351 /
G:(DE-HGF)POF4-352},
experiment = {EXP:(DE-2719)DELCODE-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34924387},
doi = {10.3233/JAD-215196},
url = {https://pub.dzne.de/record/163503},
}