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@INPROCEEDINGS{Teipel:283087,
author = {Teipel, Stefan J. and Baena, Ana Y and He, Bing and
Martinez, Lusiana and Niño, David Fernando Aguillón and
Quiroz, Yakeel T. and Grazia, Alice},
title = {{T}halamus but not basal forebrain and hippocampus atrophy
in prodromal carriers of the {C}olumbian mutation for
autosomal dominant {A}lzheimer’s disease – a {B}ayesian
confirmatory analysis},
journal = {Alzheimer's and dementia},
volume = {21},
number = {S7},
issn = {1552-5260},
reportid = {DZNE-2025-01494},
pages = {e108535},
year = {2025},
abstract = {Background:In sporadic Alzheimer's Disease (AD), the
cholinergic basal forebrain degenerates early, but seems to
be preserved in the Colombian PSEN1-E280A genetic mutation
for familial AD. In two cross-sectional studies analyzing
basal forebrain volume and connectivity from the API
Colombia cohort, we found no reduction in basal forebrain
volume or connectivity in carriers, but observed reduced
thalamic volume. Confirming these findings in other groups
with the same genetic mutation, such as those in the
Colombia-Boston (COLBOS) biomarker study, will help
determine whether the new hypothesis about basal forebrain
preservation in familial AD holds true.Method:We used
multi-modal imaging (MRI, amyloid and tau-PET) data of 57
cognitively unimpaired individuals from the COLBOS study
comprising PSEN1-E280A carriers (n = 27) and non-carriers (n
=30). Staging of functional impairment was done using the
Functional Assessment Staging Tool (FAST). Volumetry
analyses were performed using basal forebrain, hippocampus
and thalamus as regions of interest. We used Bayesian
multiple regression with both flat and informed priors to
test the hypothesis of preservation. As a secondary
analysis, we investigated the associations of amyloid and
tau pathology with brain volumes.Result:We found evidence
for no effect of mutation carrier status on basal forebrain
volume (BF₁₀: flat = 0.076; inf =0.54) and hippocampal
volume (BF₁₀: flat =0.16; inf =1.05). In contrast, we
observed moderate evidence for an effect of mutation carrier
status on thalamus volume, with smaller volumes in mutation
carriers (BF₁₀: flat =5.42; inf =8.74) (Figure 1).
Lastly, we found strong evidence against an effect of
amyloid status on basal forebrain and hippocampus, but
moderate evidence for an effect on thalamic volume (Figure
2A). Similarly, tau pathology was not associated with basal
forebrain, but showed associations with thalamus and
hippocampus. (Figure 2B).Conclusion:Our findings show that
in the PSEN1-E280A cohort, the cholinergic basal forebrain
and hippocampus are not affected early in the disease,
whereas the thalamus is, pointing to important
considerations for treatment target selection in this group.
These results should be further explored in other autosomal
dominant AD mutations.},
month = {Jul},
date = {2025-07-27},
organization = {Alzheimer’s Association
International Conference, Toronto
(Canada), 27 Jul 2025 - 31 Jul 2025},
cin = {AG Teipel},
ddc = {610},
cid = {I:(DE-2719)1510100},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
doi = {10.1002/alz70861_108535},
url = {https://pub.dzne.de/record/283087},
}