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@INPROCEEDINGS{Beer:1030443,
author = {Beer, Simone and Elmenhorst, David and Bischof, Gerard
Nisal and Ramirez, Alfredo and Bauer, Andreas and Drzezga,
Alexander},
title = {{E}xplainable {AI} identifies an {AQP}4 polymorphism-based
risk score associated with brain amyloid burden},
reportid = {FZJ-2024-05304},
year = {2024},
abstract = {Aquaporin-4 (AQP4) is an integral component of the
glymphatic system. Evidence exists that genetic variation of
AQP4impacts Aβ clearance, clinical outcome in Alzheimer’s
disease as well as sleep measures. We examined whether a
risk scorecalculated from several AQP4 single-nucleotide
polymorphisms (SNPs) is related to Aβ neuropathology
measured by[18F]Florbetapir PET in older cognitively
unimpaired individuals. In a rst step we used a machine
learning approach withdecision tree ensembles and
explainable articial intelligence (AI), namely SHapley
Additive exPlanations (SHAP), to extractinformation on
synergistic effects of AQP4 SNPs on brain amyloid burden
from the Alzheimer's Disease NeuroimagingInitiative (ADNI)
cohort. From this information, we formulated a
sex-specic AQP4 SNP-based risk score and evaluated it
onthe basis of data from the screening process of the
Anti-Amyloid Treatment in Asymptomatic Alzheimer’s
(A4/LEARN) study.We found in both cohorts signicant
associations of the risk score with brain amyloid burden
(multiple linear regression;ADNI females: p=0.001 , males:
p=0.005; A4/LEARN females: p=0.014, males: p=0.102) and
amyloid positivity (Cochran-Armitage trend test; ADNI
females: p=0.002 , males: p=0.0007; A4/LEARN females:
p=0.006, males: p=0.02). The resultssupport the hypothesis
of an involvement of the glymphatic system, and particularly
AQP4, in brain amyloid aggregationpathology. They suggest
also that different AQP4 SNPs exert a synergistic effect on
the build-up of brain amyloid burden.},
month = {Jun},
date = {2024-06-17},
organization = {Lund Glymphatic symposium, Lund
(Sweden), 17 Jun 2024 - 20 Jun 2024},
subtyp = {After Call},
cin = {INM-2},
cid = {I:(DE-Juel1)INM-2-20090406},
pnm = {5253 - Neuroimaging (POF4-525) / 5252 - Brain Dysfunction
and Plasticity (POF4-525) / 5254 - Neuroscientific Data
Analytics and AI (POF4-525)},
pid = {G:(DE-HGF)POF4-5253 / G:(DE-HGF)POF4-5252 /
G:(DE-HGF)POF4-5254},
typ = {PUB:(DE-HGF)6},
url = {https://juser.fz-juelich.de/record/1030443},
}