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@ARTICLE{Millar:266753,
author = {Millar, Peter R and Gordon, Brian A and Wisch, Julie K and
Schultz, Stephanie A and Benzinger, Tammie Ls and Cruchaga,
Carlos and Hassenstab, Jason J and Ibanez, Laura and Karch,
Celeste and Llibre-Guerra, Jorge J and Morris, John C and
Perrin, Richard J and Supnet-Bell, Charlene and Xiong,
Chengjie and Allegri, Ricardo F and Berman, Sarah B and
Chhatwal, Jasmeer P and Chrem Mendez, Patricio A and Day,
Gregory S and Hofmann, Anna and Ikeuchi, Takeshi and Jucker,
Mathias and Lee, Jae-Hong and Levin, Johannes and Lopera,
Francisco and Niimi, Yoshiki and Sánchez-González, Victor
J and Schofield, Peter R and Sosa-Ortiz, Ana Luisa and
Vöglein, Jonathan and Bateman, Randall J and Ances, Beau M
and McDade, Eric M},
collaboration = {Network, Dominantly Inherited Alzheimer},
title = {{A}dvanced structural brain aging in preclinical autosomal
dominant {A}lzheimer disease.},
journal = {Molecular neurodegeneration},
volume = {18},
number = {1},
issn = {1750-1326},
address = {London},
publisher = {Biomed Central},
reportid = {DZNE-2024-00016},
pages = {98},
year = {2023},
abstract = {'Brain-predicted age' estimates biological age from
complex, nonlinear features in neuroimaging scans. The brain
age gap (BAG) between predicted and chronological age is
elevated in sporadic Alzheimer disease (AD), but is
underexplored in autosomal dominant AD (ADAD), in which AD
progression is highly predictable with minimal confounding
age-related co-pathology.We modeled BAG in 257
deeply-phenotyped ADAD mutation-carriers and 179
non-carriers from the Dominantly Inherited Alzheimer Network
using minimally-processed structural MRI scans. We then
tested whether BAG differed as a function of mutation and
cognitive status, or estimated years until symptom onset,
and whether it was associated with established markers of
amyloid (PiB PET, CSF amyloid-β-42/40), phosphorylated tau
(CSF and plasma pTau-181), neurodegeneration (CSF and plasma
neurofilament-light-chain [NfL]), and cognition (global
neuropsychological composite and CDR-sum of boxes). We
compared BAG to other MRI measures, and examined
heterogeneity in BAG as a function of ADAD mutation
variants, APOE ε4 carrier status, sex, and
education.Advanced brain aging was observed in
mutation-carriers approximately 7 years before expected
symptom onset, in line with other established structural
indicators of atrophy. BAG was moderately associated with
amyloid PET and strongly associated with pTau-181, NfL, and
cognition in mutation-carriers. Mutation variants, sex, and
years of education contributed to variability in BAG.We
extend prior work using BAG from sporadic AD to ADAD, noting
consistent results. BAG associates well with markers of
pTau, neurodegeneration, and cognition, but to a lesser
extent, amyloid, in ADAD. BAG may capture similar signal to
established MRI measures. However, BAG offers unique
benefits in simplicity of data processing and
interpretation. Thus, results in this unique ADAD cohort
with few age-related confounds suggest that brain aging
attributable to AD neuropathology can be accurately
quantified from minimally-processed MRI.},
keywords = {Humans / Alzheimer Disease / Amyloid beta-Peptides:
metabolism / Brain: metabolism / Amyloid / Aging /
Biomarkers / Positron-Emission Tomography / tau Proteins:
genetics / tau Proteins: metabolism / Alzheimer disease
(Other) / Brain aging (Other) / Machine learning (Other) /
Structural MRI (Other) / Amyloid beta-Peptides (NLM
Chemicals) / Amyloid (NLM Chemicals) / Biomarkers (NLM
Chemicals) / tau Proteins (NLM Chemicals)},
cin = {AG Jucker / Clinical Research (Munich)},
ddc = {570},
cid = {I:(DE-2719)1210001 / I:(DE-2719)1111015},
pnm = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38111006},
pmc = {pmc:PMC10729487},
doi = {10.1186/s13024-023-00688-3},
url = {https://pub.dzne.de/record/266753},
}